The development of antibiotics is considered among the most important advances of modern science. Antibiotics have saved millions of lives. However, antimicrobial resistance (AMR) threatens this progress and presents significant risks to human health.To identify factors associated with AMR, the current epidemiology of important resistant organisms, and possible solutions to the AMR problem.PubMed (2000-2016), NIH REPORTER, and ClinicalTrials.gov databases were searched for articles and entries related to AMR, focusing on epidemiology, clinical effects of AMR, discovery of novel agents to treat AMR bacterial infections, and nonpharmacological strategies to eliminate or modify AMR bacteria. In addition to articles and entries found in these databases, selected health policy reports and public health guidance documents were reviewed. Of 217 articles, databases, and reports identified, 103 were selected for review.The increase in AMR has been driven by a diverse set of factors, including inappropriate antibiotic prescribing and sales, use of antibiotics outside of the health care sector, and genetic factors intrinsic to bacteria. The problem has been exacerbated by inadequate economic incentives for pharmaceutical development of new antimicrobial agents. A range of specific AMR concerns, including carbapenem- and colistin-resistant gram-negative organisms, pose a clinical challenge. Alternative approaches to address the AMR threat include new methods of antibacterial drug identification and strategies that neutralize virulence factors.Antimicrobial resistance poses significant challenges for current clinical care. Modified use of antimicrobial agents and public health interventions, coupled with novel antimicrobial strategies, may help mitigate the effect of multidrug-resistant organisms in the future.