Immunosuppression is the mainstay of treatment for myasthenia gravis (MG). In this paper, we review the mechanisms of action and clinical application of corticosteroids and different classes of immunosuppressive drugs that are currently used in MG patients, and present the results of their use in more than 1000 patients with MG seen at our two centers. Immunosuppressive treatment was considered along with, or as an alternative to thymectomy in MG patients with disabling weakness, not adequately controlled with anticholinesterase drugs. Overall, 82% of our patients received immunosuppressants for at least 1 year, with frequencies varying according to disease severity, from 93-95% of those with thymoma or MuSK antibodies to 72% in ocular myasthenia. Prednisone was used in the great majority of patients, azathioprine was the first-choice immunosuppressant; mycophenolate mofetil and cyclosporine were used as second-choice agents. All clinical forms of MG benefited from immunosuppression: the rate of remission or minimal manifestations ranged from 85% in ocular myasthenia to 47% in thymoma-associated disease. Treatment was ultimately withdrawn in nearly 20% of anti-AChR positive early-onset patients, but in only 7% of thymoma cases. The risk of complications appears to depend on drug dosage, treatment duration, and patient characteristics, the highest rate of serious side effects (20%) having been found in late-onset MG and the lowest (4%) in early-onset disease. Although nonspecific, current immunosuppressive treatment is highly effective in most MG patients. Lack of randomized evidence, the need for prolonged administration, and unwanted effects are still relevant limitations to its use.