There is enthusiasm to develop a transcatheter mitral valve replacement (TMVR) solution for functional mitral regurgitation (MR). The transapical (TA) approach provides a “straight shot” through the mitral from the left ventricular side. Newer technology with smaller and more complex, steerable delivery systems is emerging, allowing TMVR via the transfemoral vein/transseptal (TS) access. This chapter aims to describe TA and TS techniques and reviews the relative merits of each approach in context of the currently available MV technology. The TA approach is the most common technique currently used in TMVR. There are many different techniques for TS crossing. We perform TS crossing under guidance of transesophageal echocardiogram or intracardiac echocardiography and fluoroscopy. The procedure can be performed with conscious sedation only or with general anesthesia and endotracheal intubation.