Currently the data from 12 randomised phase III trials investigating the role of interferon-alpha (IFNα) in patients with stage II-III high-risk melanoma are available. The most prominent differences between these trials concern the dose of IFNα, the duration of IFNα administration, and the stage of disease. Some of these trials have not yet reached maturity, but despite this the positive results from some immature trials have attracted considerable attention. When only data from mature trials is considered, one may conclude that the use of high-dose IFNα does prolong disease-free survival (DFS) but not overall survival (OS). Combined data from low-dose IFNα trials does not suggest a benefit in either DFS or OS. A trial with intermediate-dose IFNα is still immature. Therefore currently the routine use of IFNα cannot be recommended outside the scope of clinical trials.