Vaccination strategies for lymphomas were developed along with one of the first recognized tumor-specific targets, the clonal antigen receptor, composed of unique variable regions known as idiotypes. Human clinical trials of idiotype vaccination have benefited from highly concordant animal models, leading to sequential improvements in design. Evidence of the clinical benefit of idiotype vaccines is strong but formally unproven. Significant progress has been made in our understanding of the basic mechanisms underlying the induction of immune responses, which has led to a proliferation of rationally designed immunotherapeutic strategies. Current research efforts include the development of more convenient methods to produce individual idiotype vaccines, the establishment of definitive proof for clinical efficacy, and the implementation of alternative vaccination strategies, including genetic vaccination and genetically or immunologically modified autologous tumor cells and dendritic cells.