Progression of degenerative mitral regurgitation (MR) leads to irreversible cardiac damage. Therefore, longitudinal follow up to determine the optimal timing of surgery is critical. Current data indicates that in addition to the standard of care—assessing for symptoms and signs of left ventricular (LV) decompensation with routine echocardiography—serial measurement of natriuretic peptides offers a quantitative means to identify patients who may benefit from closer supervision, if not surgery. Natriuretic peptide levels, and specifically changes from baseline, identify both symptomatic patients and others likely to develop cardiac dysfunction. Moreover, because natriuretic peptides are complimentary to the echocardiographic assessment of MR. Finally, changes in natriuretic peptides levels are predictive of pre- and post-operative outcomes. In short, natriuretic peptides add objectivity to the management of degenerative MR, which may aid practitioners in identifying patients who could benefit from intensive monitoring, stress testing, and perhaps mitral surgery.