The introduction of novel antimyeloma therapies, including thalidomide, lenalidomide, and bortezomib, has expanded treatment options for patients with this disease. These compounds have altered the natural history of multiple myeloma, resulting in substantial improvements in patient outcomes. However, like with any other drug, their use is associated with a specific toxicity profile. The major adverse events (AEs) associated with lenalidomide include: hematological toxicities (myelosuppression), mainly neutropenia, venous thromboembolism, gastrointestinal disturbance, skin toxicity, atrial fibrillation, asthenia, and decreased peripheral blood stem cell yield during stem cell collection when lenalidomide is used after a long period of time. These AEs are predictable, consistent, and manageable with patient monitoring, supportive care, and dose adjustment. In this article, using three clinical cases as examples, we discuss the diagnoses and management of the most frequent AEs associated with lenalidomide treatment in patients with multiple myeloma.