Percutaneous intervention for mitral valve (MV) disease has been established as an alternative to open surgical MV repair in patients with prohibitive surgical risk. Multiple percutaneous approaches have been described and are in various stages of development. Edge-to-edge leaflet plication with the MitraClip (Abbott, Menlo Park, CA) is currently the only Food and Drug Administration-approved device specifically for primary or degenerative lesions. Use of the edge-to-edge clip for secondary mitral regurgitation is currently under investigation and may result in expanded indications. Echocardiography has significantly increased our understanding of the anatomy of the MV and provided us with the ability to classify and quantify the associated mitral regurgitation. For percutaneous interventions of the MV, transesophageal echocardiography imaging is used for patient screening, intraprocedural guidance, and confirmation of the result. Optimal outcomes require the echocardiographer and the proceduralist to have a thorough understanding of intra-atrial septal and MV anatomy, as well as an appreciation for the key points and potential pitfalls of each of the procedural steps. With increasing experience, more complex valvular pathology can be successfully percutaneously treated. In addition to two-dimensional echocardiography, advances in three-dimensional echocardiography and fusion imaging will continue to support the refinement of current technologies, the expansion of clinical applications, and the development of novel devices.