Transcatheter mitral valve replacement (TMVR) using the SAPIEN platform has been performed in failed bioprosthetic valves (valve-in-valve), surgical annuloplasty rings (valve-in-ring), and native valves with mitral annular calcification (MAC) (valve-in-MAC). Experience over the past decade has identified important challenges and solutions to improve clinical outcomes. In this review, we discuss the indication, trend in utilization, unique challenges, procedural planning, and clinical outcomes of valve-in-valve, valve-in-ring, and valve-in-MAC TMVR.