In some ways, precision has been a goal for medicine since its first inception. Swallow this herb for a headache, but rub that poultice on a sore foot. Different ailments, everyone realized, require tailored treatments to be effective. As understanding of biological complexity improved, especially with the breakthrough of genetic sequencing, we gained a new dimension of potential precision: treatments might be specified, not only to a particular illness, but also to a particular person. The notion that we might be able to deliver the right drug to the right person at the right time has spurred intensive research efforts, not the least of which is the Precision Medicine Initiative, announced by US President Obama in 2015. This push to advance personalized medicine included more than US$200 million in funding, the largest chunk of which (US$70 million) was devoted to oncology. Indeed, cancer is perhaps the most obvious target for a personalized approach to therapy: tumors have particular genetic signatures that make them more or less likely to respond to one drug versus another. However, there are other diseases that might benefit from an individualized approach, as well as nongenetic strategies to make medicine more precise. This special issue of Trends in Pharmacological Sciences (TiPS) takes a broad look at the concept of precision medicine: how it is being applied across various diseases and during drug development to improve targeted treatments. We look at moving beyond oncology and also examine ethical challenges in the implementation of personalized medicine.To kick off the topic, we have a couple of short pieces on hot ideas in precision medicine. Eric Lai, from Takeda Pharmaceuticals, provides his thoughts on what it will take to expand the use of personalized medicine beyond cancer. Later, David Strauss and Ksenia Blinova, from the US FDA highlight the potential of ‘clinical trials in a dish’, in which patients’ cells take the place of actual patients during parts of the drug development process.The reviews section begins with the most mature area of precision medicine, that of oncology. We have several excellent papers that probe successes and remaining hurdles in the application of precision medicine for cancer. First, Xiaolan Deng and Yusuke Nakamura provide an overview of what they are calling the ‘Cancer Precision Medicine (CPM)’ system for patients with cancer. The CPM system covers a range of cancer management, including cancer screening, monitoring relapse and/or recurrence, selection and/or prediction of effective drug and/or treatment, and personalized immunotherapy. In a related paper, Dearbhaile Collins, Raghav Sundar, Joline Lim, and Timothy Yap discuss how advances in companion biomarker development, novel methods of serial tumor assessments, and innovative trial designs are acting synergistically to further precision medicine. They highlight how large-scale data-sharing and collaborative networks using next-generation sequencing platforms can assist in tackling challenges such as tumor heterogeneity and improved biomarkers. Finally, Nicholas Dracopoli and Mark Boguski review the key role of companion diagnostic tests in the application of precision medicine for patients with cancer. These are the tests to determine which patients might (or might not) benefit from a particular treatment and, without such analyses, personalized medicine cannot move forward. Only ∼10% of the 167 oncology drug approvals since 1998 have associated companion diagnostic tests, and development of improved companion diagnostics is crucial, especially for emerging immunotherapies.The concept of precision medicine is increasingly being applied to areas of medicine beyond oncology. For example, smoking-cessation outcomes are known to be influenced by genetic factors, including genetic variation in enzymes that metabolize nicotine and smoking-cessation medications, as well as in receptor targets for nicotine and treatment medications. In this special issue, Rachel Tyndale and Meghan Chenoweth discuss how genetic variation in the pharmacological targets of nicotine and smoking-cessation medication could be used to tailor smoking-cessation therapy, increase quit rates, and reduce tobacco-related harm. Next, Jamie Timmons examines the topic of precision medicine as it might be applied to aging: namely, if biomarkers of ‘biological age’ can be separated from chronological age, they may prove vital to the development and deployment of drugs aimed at increasing healthy human years.An additional layer of individual complexity comes not from our DNA but from the DNA of the microbes living within us. These microbes have key roles in immunity and metabolism. In their review, Jack Gilbert and Thomas Kuntz discuss how the microbiome can be both readily assayed through DNA sequencing and directly modified by various targeted interventions, making it potentially a crucial player in precision medicine.Precision medicine can also reduce harm to patients by steering them away from drugs that they might adversely react to. Adverse drug reactions (ARDs) remain a large problem and are associated with increased mortality and high costs to healthcare systems. Ana Alfirevic and Munir Pirmohamed discuss how genomic testing can help predict and prevent ADRs, as well as be used in other ways such as diagnosis, closer monitoring of those at risk, pre-emptive genotyping, and understanding of mechanism, all of which will improve the benefit:risk ratio of drugs.Another way that medicine is becoming increasingly precise is through improved targeting of receptor subtypes and particular signaling pathways. For example, a major issue in clinical endocrinology today is how to use hormones to achieve the health benefits they clearly can provide but avoid the adverse effects of these hormones. Selective targeting of hormone receptor subtypes is one attractive way to harness the beneficial effects of hormones while reducing adverse effects, thereby making the treatment more precise. Margaret Warner, Bo Huang, and Jan-Ake Gustafsson highlight estrogen receptor beta, which has promise as a selective target in hormone replacement therapy, and in breast and prostate cancers.Finally, although hardly least important, is consideration of ethical issues related to the implementation of personalized medicine, which includes everything from how clinical testing is performed to patient access to these individualized treatments. Wylie Burke, Diane M. Korngiebel, and Kenneth Thummel examine some of the challenges involved, including the limited evidence base and lack of data from diverse populations, prioritizing research accordingly using procedures that enhance the trustworthiness of clinical practice guidelines, and creating decision support for clinicians and patients that addresses their needs.We at TiPS would like to thank all the authors for their great contributions to this special issue, as well as the referees whose counsel helped to strengthen the pieces along the way. We hope that you find the resulting array articles to be insightful, forward-thinking, and a pleasure to read.