Personalized medicine is the customization of treatment based on a patient’s hereditary or somatic genetics and holds the promise of revolutionizing healthcare. Companion diagnostics, many of which are molecular genetics assays, are critical tools in the implementation of personalized medicine. Information derived from these tests provides for customizing specific therapies based on the genetics of the disease. While the benefits are clear, the path to a successful companion diagnostic has required a forging of new alliances between drug and diagnostic developers, clinical laboratories, physicians, pathologists, and healthcare providers. Molecular genetic companion diagnostic assays are becoming more relevant and important in an environment of increased regulatory guidance in their development and application. Here, we review key molecular genetics companion diagnostic tests and their applications in personalized medicine.