Although cancer immunotherapy was initiated by William Coley more than a century ago, the field of cancer vaccines is in an early stage of development. Only recently, major advances in cellular and molecular immunology have allowed a comprehensive understanding of the complex and high rate of interactions between the immune system and tumor cells. We have learned that these tumor-immune system interactions may result either in strong immune antitumor response or tolerance to tumor-associated antigens. This article will discuss the profound interest in cancer vaccines derived from their potential to induce antitumor responses in vivo. Substantial data from several preclinical models and early human clinical trials have confirmed the ability of cancer vaccines to induce immune responses that are tumor-specific and, in some cases, associated with clinical responses. One future challenge will be to determine how to appropriately stimulate the pathways leading to effective interaction among antigen-presenting cells, T lymphocytes, and tumor cells. It also is critical to develop monitoring strategies that may allow the identification of patients who may benefit from cancer vaccines.