Measurable (or minimal) residual disease (MRD) testing offers critical prognostic insight in multiple myeloma (MM), surpassing conventional response criteria. While bone-marrow-based assays are most commonly performed, MRD assessment in peripheral blood and advanced imaging may add complementary value. A comprehensive approach, integrating serial MRD testing across compartments, may offer the most accurate appraisal of disease burden. MRD has been validated as a surrogate endpoint for accelerated approval (AA) of MM therapies and is increasingly adopted as a key clinical trial endpoint. Ongoing phase 3 trials are using MRD status to tailor consolidation and maintenance strategies, and emerging evidence supports its role in guiding treatment de-escalation, including discontinuation of maintenance therapy. However, barriers remain to implementing MRD as a treatment goal, including cost, complexity of interpreting results, and uncertainty around the optimal timing for guiding decision-making. Moreover, there is a paucity of data on the use of MRD resurgence to prompt changes in therapy. While MRD negativity represents a compelling endpoint in both clinical practice and research, prospective randomized studies will help to better elucidate how best to incorporate MRD into the MM treatment paradigm.