Pomalidomide is an immunomodulatory drug recently approved by the US FDA and EMA for the treatment of refractory and relapsed multiple myeloma. Pomalidomide appears to be more potent and less toxic than thalidomide and lenalidomide and has proven to be effective in a proportion of patients already exposed and refractory to these agents. The approved combination of pomalidomide and weekly dexamethasone offers clinical benefit to at least one-third of patients with multiple myeloma that have failed both bortezomib and lenolidomide treatment. This review will focus on the preclinical data and clinical experience in this setting. Off-label use of pomalidomide, mainly its combination with other active drugs for multiple myeloma and the role of pomalidomide in other hematologic malignancies still remain to be explored in depth and are discussed briefly.