Immunomodulatory agents, including cytokines, monoclonal antibodies, and CpG oligonucleotides, have properties that suggest they have the ability to augment rituximab in the treatment of non-Hodgkin's lymphoma. Although several clinical trials have promising results, no randomized trials of reasonable size have been performed to date, limiting the ability to discern whether combinations of immunomodulatory agents with rituximab impact clinical outcome. Until such trials are mature, we do not recommend using these agents in combination outside of the research setting.