The novel agents bortezomib and lenalidomide improve outcomes in multiple myeloma, yet most patients will relapse after exhausting treatment. Management of relapsed and refractory multiple myeloma (RRMM) is challenging owing to disease-, patient- and treatment-related factors, and new therapies for these patients are required. Pomalidomide (POM) is an immunomodulatory compound that has been recently approved in the USA for the treatment of RRMM after two prior therapies, including lenalidomide and bortezomib. POM has several potential mechanisms of action and has a unique pharmacokinetic profile. Several trials demonstrate the efficacy and safety of POM in RRMM, including subjects refractory to lenalidomide and bortezomib. Herein, POM is reviewed as a clinically active new treatment option for RRMM.