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Bacillus Calmette Guerin (BCG) was introduced 100 years ago for vaccination against tuberculosis and 40 years ago for treatment of bladder cancer.  Yet the last decade has witnessed a surge of new uses of BCG in the prevention or treatment of autoimmune disease, allergy and respiratory disease unrelated to tuberculosis.  This article reviews the efficacy and safety of the two main uses of BCG, tuberculosis prevention and bladder cancer treatment.  It discusses the animal and human studies underlying the new uses of BCG.  Finally, it covers the two avenues of basic science propelling the new uses of BCG, both of which rely on BCG role as an inducer of the cytokine Tumor Necrosis Factor (TNF):  the selective destruction of autoreactive T-lymphocytes and the induction of T-regulatory cells.