The idiotypic determinants of B-cell lymphomas, formed by cell-specific rearrangement of the immunoglobulin genes, are unique and are therefore a suitable target against which to direct immunotherapy. Recent advances in our understanding of the fundamental mechanisms behind an effective immune response, coupled with advances in genetic engineering techniques, have led to a renewed interest in immunotherapy. Early clinical studies have confirmed the immunogenicity of the idiotypic antigen in patients with lymphoma. This review discusses the different methods of idiotypic vaccination currently under investigation in the clinic, including protein, genetic, and cellular vaccines. Protein vaccines are the most clinically advanced, with phase III trials of idiotypic protein linked to GM-CSF currently underway. DNA vaccines are easier to produce but to date only appear to be weakly immunogenic in man. Dendritic cell vaccines have shown promise but their use may be limited by the complexity of this approach. This review also highlights other approaches not yet in the clinic but that have shown promise in the laboratory, such as viral vaccines and T-cell therapy. © 2005 Adis Data Information BV. All rights reserved.