Personalized medicine has gained significant attention over the last decade as technologies for understanding biological differences between individuals have advanced dramatically. There are many potential benefits of personalized medicine including minimizing risk of drug toxicity, increasing benefit from drugs used, contributing to the sustainability of the healthcare system and facilitating drug discovery and development programs. Unfortunately there are also many barriers such as cost, complexity, high quality evidence requirements, and the need for further education that have limited the clinical translation of pharmacogenomic tests to date. Issues that need to be clarified are also considered, such as the regulatory evidence requirements for pharmacogenomic tests and the need for multiple pathways and for pharmacogenomic marker development. These issues surrounding personalized medicine are contextualized using three contemporary examples of pharmacogenetic tests involving drug metabolising enzymes: UDP glucuronosyltransferase 1A1 and irinotecan toxicity, cytochrome P450 2C19 and clopidogrel efficacy, and cytochrome P450 2C9 and warfarin dosing.