Cancer vaccines are at the forefront of novel, targeted approaches to cancer treatment. Low toxicity, the potential for circumventing drug cross-resistance, and the potential for persistence of the antitumor effect due to immunologic memory represent a mandate for accelerated clinical development. Advances in molecular immunology have suggested approaches for overcoming the formidable mechanisms of immune tolerance that are pre-established in cancer patients, and many have already been tested in preclinical models. Also, early studies revealed that not all tumor antigens are created equal, and identifying those capable of eliciting immune-mediated tumor rejection is essential to the development of effective recombinant cancer vaccines. While early trials have generally resulted in disappointing clinical outcomes, they have yielded insight into the critical parameters for the design of cancer vaccine trials and provided powerful reagents for tumor antigen identification. By utilizing the lessons learned from the research laboratory and these early clinical trials, informative second generation vaccine trials should have a high likelihood of success. Clinical protocols that consider how best to incorporate therapeutic cancer vaccines into the current standard of care should allow cancer vaccines to take their place alongside traditional cancer treatment modalities in oncology practice.