Recently, immunotherapy has been widely investigated for the treatment of cancer. While much of the success in this area lies with passive immunotherapy, the focus of this review is active vaccination strategies, which are showing promise. Cancer cells express a wide profile of different proteins, some of which are related to oncogenic transformation and are specific to cancer cells only. However, in cancer, most protein targets presented to the immune system from tumor cells are self-antigens. The immune system is highly tolerant of, and therefore does not react to, these self-antigens. Active immunotherapy aims to reverse this immune tolerance so the immune system can respond appropriately to self-antigens. To generate a successful antitumor response, several features should be considered: a target antigen on tumor cells to direct the immune response, a platform to present the vaccine-derived antigen to the immune system, an adjuvant to enhance immune stimulation, and appropriate monitoring techniques. New tools are becoming available for monitoring, although the clinical relevance for these assays needs to be established. Optimism for cancer vaccine approaches are increasing. Recent studies have shown that it is possible to break immune tolerance to self-antigens. Promising therapeutic clinical activity has been demonstrated, and other studies have shown that cancer vaccines are most beneficial for minimal residual disease states. Further optimization of cancer vaccines and larger clinical studies are required.