As treatment regimens have emerged that increase the proportion of patients with lymphoma achieving responses to therapy, maintenance regimens have followed to provide means for improving progression-free survival and overall survival for responders. An ideal maintenance regimen would have limited toxicity, be easy to administer, and demonstrate a survival benefit over administration of the same agent in the relapsed disease setting. Numerous phase II and randomized trials are now maturing that examine the benefits of maintenance therapies for indolent and aggressive lymphomas. We provide a comprehensive review of existing data describing the shortcomings and benefits of interferon maintenance and rituximab maintenance therapies for patients with non-Hodgkin lymphoma (NHL). Notably, rituximab maintenance has demonstrated benefits for patients with follicular lymphoma after CVP (cyclophosphamide/vincristine/prednisone) induction therapy and after rituximab-containing chemotherapy combinations at relapse. Benefits have also been demonstrated in diffuse large B-cell lymphoma after CHOP (cyclophosphamide/doxorubicin/vincristine/prednisone) induction but not after R-CHOP (rituximab plus CHOP) induction. Randomized trials in patients with mantle cell lymphoma demonstrate a benefit for rituximab maintenance after R-FCM (fludarabine/cyclophosphamide/mitoxantrone plus rituximab) chemoimmunotherapy but not after single-agent rituximab. Further studies are needed to characterize the benefits of other agents in maintenance therapy and other strategies for maintaining remissions for patients with NHL.