Pharmacogenomic testing has the potential to greatly benefit patients by enabling personalization of medication management, ensuring better efficacy and decreasing the risk of side effects. However, to fully realize the potential of pharmacogenomic testing, there are several important issues that must be addressed. Areas covered: In this expert review we discuss current challenges impacting the implementation of pharmacogenomic testing in the clinical practice. We emphasize issues related to testing methods, reporting of the results, test selection, clinical interpretation of the results, cost-effectiveness, and the long-term use of pharmacogenomic results in clinical practice. We identify opportunities and future directions to facilitate clinical implementation. Expert commentary: Several key elements are necessary to optimally integrate pharmacogenomic testing into clinical practice. Collaborative efforts among laboratories are needed to improve standardization of testing and reporting of the results. Clinicians need educational opportunities to improve understanding of which test to order and how to interpret the results. The electronic health records and other clinical systems need to improve their storage of the pharmacogenomics test results and interoperability to facilitate the use of clinically actionable results to improve patient care.