The probability of success of developing medicines to treat human disease can be improved by leveraging human genetics. Different types of genetic data and techniques, including genome-wide association, whole-exome sequencing, and whole-genome sequencing, can be used to gain insight into human disease. Layering different types of genetic evidence from Mendelian disease, coding variants, and common variation can bolster support for a genetic target. Human knockouts offer the potential to perform reverse genetic screens in humans to identify physiologically relevant targets.