Early trials of Bacillus Calmette-Guérin (BCG)-based immunotherapy for melanoma consistently show a trend toward improved clinical outcomes in patients treated with BCG compared with observation alone. As an extension of these findings, investigators have initiated the Malignant Melanoma Active Immunotherapy (MMAIT) trials in patients with stage III (MMAIT-III) and stage IV (MMAIT-IV) disease. The overall survival of the patients receiving BCG plus placebo was much better than expected in both studies, thus suggesting a potential for BCG as an adjuvant after the resection of advanced disease. The work contained herein will explore the clinical rationale for adjuvant BCG in future trials focused on the treatment of patients with advanced malignant melanoma.