Patients with thick primary melanomas or regional lymph node involvement are at high risk of relapse. Investigations of adjuvant therapy over the past 30 years show only one significantly positive trial employing high dose interferon-alpha-2b. This is a potentially toxic regimen, therefore, other better-tolerated forms of adjuvant immunotherapy are being studied. Recent advances in basic science have led to a better understanding of the T-cell response to human cancer. This article discusses the background and current clinical trials of active specific immunotherapies for melanoma, including peptide and ganglioside vaccines.