The development of cancer vaccines, aimed to enhance the immune response against a tumor, is a promising area of research. A better understanding of both the molecular mechanisms that govern the generation of an effective immune response and the biology of a tumor has contributed to substantial progress in the field. Areas of intense investigation in cancer immunotherapy will be discussed here, including: (1) the discovery and characterization of novel tumor antigens to be used as targets for vaccination; (2) the investigation of different vaccine-delivery modalities such as cellular-based vaccines, protein- and peptide-based vaccines, and vector-based vaccines; (3) the characterization of biological adjuvants to further improve the immunogenicity of a vaccine; and (4) the investigation of multimodal therapies where vaccines are being combined with other oncological treatments such as radiation and chemotherapy. A compilation of data from preclinical studies conducted in vitro as well as in animal models is presented here. The results from these studies would certainly support the development of new vaccination strategies toward cancer vaccines with enhanced clinical efficacy.