Thalidomide possesses potent anti-inflammatory, immunomodulatory, and antiangiogenic properties. Thalidomide combined with corticosteroids is therapeutically active in multiple myeloma and myelofibrosis (MF). Lenalidomide and pomalidomide are second-generation immunomodulatory drugs (IMiDs) that were created by chemical modification of thalidomide with the intent to reduce toxicity and enhance therapeutic activity. Both drugs have also been shown to be active in the treatment of myeloma and MF. Thalidomide is US Food and Drug Administration (FDA)-approved for use in acute erythema nodosum leprosum and, in combination with dexamethasone, in newly diagnosed myeloma. Lenalidomide is approved for use in low/intermediate-1 risk myelodysplastic syndromes associated with transfusion-dependent anemia and a deletion 5q cytogenetic abnormality and, in combination with dexamethasone, in relapsed myeloma. Pomalidomide is currently not FDA-approved. Herein, we summarize what is currently known about the biologic and therapeutic effects of pomalidomide.