The development of vaccines for treating cancer is discussed. The central hypothesis behind active specific immunotherapy for cancer is that tumor cells express unique antigens that tell the immune system that something about these cells is foreign. A vaccine is a way of delivering an antigen to the immune system such that immune cells recognize the antigen as foreign and destroy any cells bearing that antigen. Early trials of vaccines for treating cancer were limited by technical problems related to poor knowledge of the immune system. Recent research has focused on expression on the surfaces of antigen-presenting cells of antigenic peptides bound to major histocompatibility complex (MHC) molecules, peptide recognition by cytotoxic T cells, and the requirement for a second signal, such as the costimulatory molecule B7, for T-cell activation. Antigenic peptides constitute the "keys" that open the "locks" of T cells; the problem is that researchers have difficulty choosing the right keys from among the myriad available. Administering an adjuvant enhances the immune response by making the antigen more recognizable as foreign. Vaccine preparation techniques include peptide pulsing (a method for bosting cell-surface expression of the antigenic peptide-MHC combinations), intramuscular injections of DNA plasmids encoding the desired antigen, and gene insertion into vaccinia virus by recombinant DNA technology. Cancer vaccines may be administered by scarification, by subcutaneous and intramuscular injection, and intranasally. Clinical trials of cancer vaccines continue to encounter problems because of the many variables in administration routes, dosages, patient populations, and methods for evaluating responses. There have been some promising results but also many treatment failures. Antigen targets in trials today include normal antigens that have a limited normal-tissue distribution or expression (e.g., carcinoembryonic antigen), viral proteins (e.g., E6 protein of human papillomavirus), and mutated oncogenes. Toxicities have been mild. Better understanding of the immune system and better technology have led to advances in the development of vaccines for treating cancer, but there is still much progress to achieve.