Immunosuppressive agents serve a major role in the management of once-fatal conditions such as the systemic necrotizing vasculitides, but they are also being used in more common, chronic inflammatory disorders such as rheumatoid arthritis. The drugs are all capable of reducing cell division but they differ in their modes of action. This is in keeping with their differing rates of action, and different indications. Azathioprine is a valuable alternative to slow-acting antirheumatic drugs in older patients with rheumatoid arthritis. Cyclophosphamide has transformed the outlook of many forms of vasculitis. Chlorambucil is particularly useful in improving the prognosis for children with amyloidosis secondary to juvenile chronic arthritis. We have tried to highlight the role of these drugs in a number of rheumatic diseases. We have emphasized their clinical applications, with some laboratory evidence for their effects. The major side-effects are reviewed. Finally, we have discussed their possible mechanisms of action.