The results from these phase II studies demonstrate the activity of oral lenalidomide monotherapy in patients with relapsed or refractory aggressive NHL and warrant further investigation of lenalidomide therapy, alone or in combination, in the treatment of patients with aggressive NHL. It was recently reported that when used in combination, lenalidomide (maximum-tolerated dose [MTD] 20 mg/day, 21 of 28 days) and rituximab produce a robust response rate in relapsed or refractory mantle cell lymphoma, with a favourable toxicity profile. In multiple myeloma (MM) patients, several phase 1/2 trials have evaluated lenalidomide in conjunction with chemotherapy, such as melphalan and prednisone (MTD 10 mg/day, 21 days every 4 to 6 weeks), doxorubicin and dexamethasone (MTD 25 mg/day with G-Colony-stimulating factors (CSF), 21 of 28 days), or doxorubicin, vincristine and dexamethasone (MTD 10 mg/day, 21 days every 4 to 6 weeks). These combinations provide a considerable proportion of high-quality responses with substantial durability in patients with MM and overcomes several well-known adverse prognostic factors. A phase 1 study showed that lenalidomide can be safely combined with R-CHOP (R2CHOP) in the initial chemotherapy for aggressive B-cell lymphomas. Preliminary results of ongoing phase 2 suggest that the addition of lenalidomide to rituximab, cyclophosphamide, adriamycin, vincristine and prednisone (RCHOP) could overcome the negative prognostic impact of the non-germinal center B-cell (GCB) phenotype on outcome.