These are exciting times for the field of cancer immunotherapy. Although the clinical efficacy of monoclonal antibodies has been demonstrated since the early 1990s, the therapeutic profile of other immunotherapeutic approaches—especially vaccines—has not yet been formally clarified. However, the recent success of several immunotherapeutic regimens in cancer patients has boosted the development of this treatment modality. These achievements stemmed from recent scientific advances demonstrating the tolerogenic nature of cancer and the fundamental role of the tumor immune microenvironment in the suppression of antitumor immunity. New immunotherapeutic strategies against cancer attempt to promote protective antitumor immunity while disrupting the immunoregulatory circuits that contribute to tumor tolerance. Cancer vaccines differ from other anticancer immunotherapeutics in that they initiate the dynamic process of activating the immune system so as to successfully re-establish a state of equilibrium between tumor cells and the host. This article reviews recent clinical trials involving several different cancer vaccines and describes some of the most promising immunotherapeutic approaches that harness antitumor T-cell responses. In addition, we describe strategies whereby cancer vaccines can be exploited in combination with other therapeutic approach to overcome—in a synergistic fashion—tumor immunoevasion. Finally, we discuss prospects for the future development of broad spectrum prophylactic anticancer vaccines.