During the past century, excite-ment has waxed and waned over the possibility that the extraordinary disease-fighting prowess of the immune system might be enlisted to destroy cancers. Today doubts have vanished, and countless investigators are working to translate the notion into potent new biological therapies. Clinical support for the idea that the immune system might restrain the development of cancer emerged in the 1800s, when physicians noticed that tumors sometimes regressed in cancer patients who contracted bacterial infections. William B. Coley, a surgeon at Memorial Hospital in New York City from 1892 to 1936, dedicated his life to creating therapies based on this observation. He made deliberate attempts to infect cancer patients with bacteria and later devised a vaccine consisting of killed bacteria to prompt a tumor-killing response. These treatments—which we would now consider immunotherapies because they aimed to attack disease with the body’s own defenses—brought about complete tumor regressions in some individuals. But they were not broadly accepted, because the results were unpredictable. Early in this century other investigators also attempted to develop immunebased therapies, but none showed a convincing benefit. Still, the link between immunity and cancer remained firmly fixed in the minds of many people. During the 1960s and 1970s, for example, there was wide acceptance of the “immunosurveillance” model put forth by Lewis Thomas of New York University and MacFarlane Burnett of the Hall Institute in Melbourne, Australia. This theory held that the immune system constantly seeks out and destroys emerging cancer cells. Tumors, it proposed, arise when this policing mechanism fails. In the following years, however, accumulating evidence suggested that the immune system attacked only tumors caused by viral infections. Because such cancers account for a minority of all cases, the theory appeared flawed. Recently, though, new insights have generated a resurgence of interest in immunotherapies for cancer. In particular, the science of immunology has undergone revolutionary changes. Researchers have discovered and isolated the cells and chemicals that enable the immune system to defend the body against attack and to prune away infected and damaged tissues. By studying these components, immunologists have gained a deep understanding of the workings of the normal immune system. And cancer immunologists have gained knowledge of mechanisms and molecules by which they may someday control cancer.