Azathioprine has been available for 30 years and is used in a variety of dermatologic conditions. In common with other systemic immunosuppressant drugs, it has potentially serious side effects in both the short and the long term. It has a favorable therapeutic ratio, however, and most side effects can be avoided by administering low doses for short periods. This review describes azathioprine's chemistry, drug interactions, adverse effects, and oncogenicity and then deals with its clinical applications. The well-established uses are discussed first, followed by less conventional ones. In severe, potentially fatal blistering diseases, azathioprine has an undisputed place in management. For intractable, disabling actinic reticuloid and atopic eczema, it has a smaller part to play, and its role is less clear.