Drug development is a costly, time-consuming, and challenging endeavour, with only a few agents reaching the threshold of approval for clinical use. Therefore, approaches to more efficiently identify targets that are likely to translate to clinical benefit are required. Interrogation of the human genome in large patient cohorts has rapidly advanced our knowledge of the genetic architecture and underlying mechanisms of many diseases, including nonalcoholic fatty liver disease (NAFLD). There are no approved pharmacotherapies for NAFLD currently. Genetic insights provide a powerful and new approach to infer and prioritise candidate drugs, with such selection avoiding myriad pitfalls, while defining likely benefits. In this review, we discuss the prospects and challenges for the optimal utilisation of genetic findings for improving and accelerating the NAFLD drug discovery pipeline.