Lenalidomide, an analog of thalidomide, is a promising new therapeutic agent that does not seem to cause significant somnolence, constipation, and neuropathy, which are usually dose-limiting for thalidomide. It has been hypothesized that the mechanism of action of lenalidomide includes immunomodulatory, antineoplastic, anti-angiogenic and pro-erythropoietic properties. Preclinical as well as clinical observations demonstrate that lenalidomide downregulates production of various critical prosurvival cytokines in the tumour microenvironment while concurrently promoting activation of T- and natural killer (NK) cell-mediated antitumour response. In aggressive lymphomas, lenalidomide was shown to exert antiproliferative activity by enhancing the expression of cell cycle regulators, including p21 and SPARC, to induce G1 cell cycle arrest, caspase activation, and apoptosis.