Lenalidomide has emerged as an effective therapeutic alternative for the management of anemia in lower-risk myelodysplastic syndromes (MDS). Compelling results from phase I and phase II clinical studies prompted the US Food and Drug Administration to approve lenalidomide for the treatment of transfusion-dependent MDS patients with interstitial deletion of chromosome 5q [del(5q)]. Subsequently, the National Comprehensive Cancer Network (NCCN) has incorporated lenalidomide into their current treatment algorithm for the treatment of lower-risk del(5q) patients. This discussion examines the current NCCN guidelines for the treatment of these patients, including the management of anemia in lower-risk MDS, and discusses the potential future therapeutic applications of lenalidomide in this disease.