Advances in the understanding of the immune response to tumors has led to the development of new strategies to design therapeutic vaccines. One of these strategies is the development of protein transfer of immunostimulatory molecules onto the surface of tumor cells, thereby directing the immune response to the tumor antigens carried by the modified tumor cells. This strategy has been developed as an alternative to gene transfer, the more classical technique of introducing immunostimulatory molecules onto tumors. In this report we briefly review current strategies for immunotherapy and then focus on several approaches to protein transfer and their historical basis. Finally, the application of these protein transfer approaches to develop cancer vaccines are reviewed and discussed.