Metformin has long been the drug of choice for treating patients with type 2 diabetes. Because of its effectiveness, safety profile, and affordability, it is used by millions of people worldwide. Emerging evidence indicates that metformin might also have antineoplastic effects in both diabetic and nondiabetic individuals. This article reviews studies that examine the potential mechanisms of action underlying the anticancer properties of metformin and discusses the possible use of this antidiabetic biguanide in the chemoprevention and treatment of head and neck cancer.