Multiple myeloma accounts for approximately 10% of hematologic malignancies.The diagnosis requires =10% clonal bone marrow plasma cells or a biopsy proven plasmacytoma plus evidence of one or more multiple myeloma defining events (MDE): CRAB (hypercalcemia, renal failure, anemia, or lytic bone lesions) features felt related to the plasma cell disorder, bone marrow clonal plasmacytosis =60%, serum involved/uninvolved free light chain (FLC) ratio =100 (provided involved FLC is =100 mg/L), or >1 focal lesion on magnetic resonance imaging.The presence of del(17p), t(4;14), t(14;16), t(14;20), gain 1q, or p53 mutation is considered high-risk multiple myeloma. Presence of any 2 high risk factors is considered double-hit myeloma; 3 or more high risk factors is triple-hit myeloma.In transplant eligible patients, induction therapy consists of bortezomib, lenalidomide, dexamethasone (VRd) given for approximately 3-4 cycles followed by autologous stem cell transplantation (ASCT). In high-risk patients, daratumumab, bortezomib, lenalidomide, dexamethasone (Dara-VRd) is an alternative to VRd. Selected standard risk patients can get additional cycles of induction, and delay transplant until first relapse. Patients not candidates for transplant are typically treated with VRd for approximately 8-12 cycles followed by lenalidomide; alternatively these patients can be treated with daratumumab, lenalidomide, dexamethasone (DRd).After ASCT, standard risk patients need lenalidomide maintenance, while bortezomib-based maintenance is needed for patients with high-risk myeloma.Most patients require a triplet regimen at relapse, with the choice of regimen varying with each successive relapse. This article is protected by copyright. All rights reserved.