In chronic autoimmune conditions such as myasthenia gravis (MG), immunosuppression--usually long-term--is often necessary. The mechanisms of action of immunosuppressant drugs in MG fall into three main categories: inhibition of the cell cycle (azathioprine, cyclophosphamide, methotrexate and mycophenolate mofetil), immunosuppression of T cells (steroids, ciclosporin and tacrolimus), and B-cell depletion (rituximab). Data on immunosuppressant drugs in MG derive mainly from clinical experience, observational studies and expert opinion. The main drawbacks of the randomized evidence are the small size of most drug trials, variations in study design, and a lack of head-to-head studies. It is therefore difficult to determine the relative efficacy of each immunosuppressant. Oral prednisolone, usually started at a low dose on an alternate-day regimen, and gradually increased, is the recommended first-choice short-term immunosuppressant. Long-term immunosuppression regimens vary between different countries and physicians. Azathioprine is often the first-choice drug for long-term immunosuppression, and it is usually started together with steroids to allow tapering of steroids to the lowest dose possible. Methotrexate, mycophenolate mofetil or tacrolimus should be considered in patients who are intolerant of or unresponsive to azathioprine. Ciclosporin and cyclophosphamide should only be considered as a last resort, as these drugs can cause serious adverse events. Data on rituximab use in MG are sparse, but the initial results are promising.