Recent advances have highlighted the importance of long-term, continuous treatment in multiple myeloma (MM) to improve survival. However, treatment burden continues to negatively impact the real-world duration of MM therapy, and strategies to limit the adverse impact of treatment on patient quality of life are therefore particularly important. Oral MM therapies include the immunomodulatory drugs lenalidomide, thalidomide, and pomalidomide; the alkylating agents melphalan and cyclophosphamide; the histone deacetylase inhibitor panobinostat; the corticosteroids prednisone and dexamethasone; and the proteasome inhibitor ixazomib. The most commonly reported adverse events with these treatments include hematologic events such as thrombocytopenia and neutropenia; the gastrointestinal events nausea, vomiting, and diarrhea; venous thrombotic events such as deep-vein thrombosis and pulmonary embolism; and events such as rash and peripheral neuropathy. It is important that patients receiving oral therapies at home report symptoms before they become difficult to manage. Appropriate management of these treatment-related adverse events, awareness of both food and drug interactions, and assisting patients with out-of-pocket costs are all important factors in providing efficacious, sustainable, and convenient MM therapy. We outline evidence-based recommendations to provide a practical guide for health care providers addressing the effective management of MM patients receiving oral therapy.