Autoimmune hepatitis is a corticosteroid-responsive liver disease arising consequent to immunogenetic and environmental risk factors. The clinical course reflects relapsing and remitting, hepatocyte targeted immunologic damage, which is countered by reparative responses to cell injury. Appropriate and timely immunosuppressive therapy drives the disease into remission, albeit with inevitable side effects. Many challenges faced in the clinic reflect practice that must capture a heterogeneous disease presentation, course, and treatment response, as well as treatment tolerability. In this Grand Round we appraise the evidence supporting current treatment approaches, address the impact of autoimmune liver disease 'crossover or overlap' presentations, explore important clinical correlates to immune-serological classifiers, and discuss the factors influencing choice of alternative therapy in difficult-to-treat situations.