Early phase clinical trials conducted 10 years ago laid foundation for use of Lenalidomide in low-risk transfusion dependent MDS patients. Lenalidomide showed promising efficacy in patients with Del 5q abnormality which is found in 2-5% of MDS patients. 65% of patients achieved RBC transfusion independence lasting for median 2 years duration. These results were subsequently confirmed in placebo-controlled phase 3 trial leading to approval of Lenalidomide in low risk MDS. Lenalidomide is associated with side effects like diarrhea while neutropenia and thrombocytopenia are observed more frequently in patients with Del 5q abnormality. P-53 & ROS mutations can impact efficacy of Lenalidomide, and blood or bone marrow based NGS is recommended to monitor evolution of disease.