Synthetic oligodeoxynucleotides containing CG motifs (CpG ODNs) have potent immunostimulatory properties, and have potential as immunotherapeutic agents in cancer. Animal models suggest that CpG ODNs may be useful as both single agents and to enhance the efficacy of monoclonal antibody therapy. CpG ODNs can also enhance the efficacy of tumor immunization through use as an immune adjuvant, to activate antigen presenting cells, or as a component of DNA vaccines. Clinical trials are now beginning to assess whether the promise of these agents in the laboratory will translate into CpG ODNs becoming a valuable component of clinical cancer immunotherapy.