Companion diagnostics (CoDx) will likely continue to rapidly increase in number and application to disease areas including solid tumors, for example EGFR for gefitinib and ALK fusion gene for crizotinib in non-small-cell lung cancer; KRAS against the use of cetuximab and panitumumab in colorectal cancer; HER2 for trastuzumab in breast cancer. CoDx are an indispensable part of personalized medicine and pharmacogenomics. In CoDx development, there are still many challenges, such as the business model promoting cooperation between diagnostics and pharmaceutical companies, and also the regulations related to CoDx. The FDA notice on the development of CoDx in 2011 recommended the co-development of a new drug and CoDx as the best practice, and the Ministry of Health, Labour and Welfare in Japan also issued a statement in 2013. In addition, the recent discovery of many novel variants in the DNA sequence, advances in sequencing and genomic technology, and improved analytic methods have enabled the impact of germline and somatic mutations to be determined using multiplex diagnosis. The complex challenges to develop CoDx necessitate a close collaboration among academic institutions, regulatory authorities, and pharmaceutical companies. [Review].