NASH is a common liver disease that increases liver-related mortality and reduces survival. The need for optimal management of NASH is therefore a priority for today's practicing hepatologist. The rationale for specific pharmacological therapy for NASH is based on the potential for disease progression and the difficulties that many patients have successfully implementing, in the long term, diet and lifestyle changes. Even in those that succeed, limited evidence exists that severe liver injury in patients with NASH can be reversed by diet and lifestyle measures alone. This Review provides a personal and critical assessment of the histological efficacy and safety of agents tested in randomized trials in patients with NASH.