Percutaneous treatment of mitral valve regurgitation with the MitraClip™ system is emerging as an alternative to surgery in high-risk and inoperable patients. The device is designed to bond the opposing leaflets at the site of regurgitation, reproducing the results of the Alfieri technique in a beating heart approach. We describe the selection criteria and the procedural steps of the procedure, which is performed under general anesthesia and guided by trans-esophageal echocardiography, using a sophisticated delivery system to deliver the clip at the desired target. We also briefly report the currently available data which supports the application of this therapy in selected patients with either degenerative or functional mitral regurgitation.