Background: Prednisone and azathioprine are effective in the treatment of autoimmune hepatitis, but diverse side effects can diminish their net benefit. Objectives: Describe the frequency and nature of these side effects and propose management strategies to minimize their impact. Methods: Pertinent articles published from 1970 to 2007 were identified by Medline search and through a personal library. Results: Medication is prematurely discontinued in 13% of patients mainly because of cosmetic changes, cytopenia, or osteopenia. Populations at high risk are the elderly, those with pre-existent co-morbidities, patients with near-zero thiopurine methyltransferase activity, individuals who are treatment-dependent, pregnant women, and asymptomatic patients who are over-treated. Conclusions: Proper patient selection, effective pre-treatment counseling, pre-emptive protective measures, realistic treatment objectives, and early identification of problematic patients can reduce complications. Individualized dosing schedules and the emergence of non-steroidal medications are realistic expectations.