Background: Transcatheter edge-to-edge repair of mitral valve (M-TEER) is reasonable consideration in symptomatic patients with severe degenerative mitral regurgitation (MR) who are at high or prohibitive risk of surgical repair or replacement. In symptomatic patients on maximally tolerated medical therapy with severe secondary MR from left ventricular systolic dysfunction, M-TEER is reasonable therapeutic option. Methods: In this review, we present a comprehensive overview of the most recent literature and considerations for M-TEER in patients excluded from key trials. These include patients with cardiogenic shock, acute ischemic MR, atrial functional MR, failed surgical mitral valve prosthesis and pulmonary hypertension. Conclusions: M-TEER is feasible and a reasonable alternative option for these patient populations with a significant clinical benefit. However, randomized clinical trials are needed to ascertain findings from these observational studies.