Mitral valve prolapse (MVP), consisting of an abnormal protrusion of mitral leaflets into the left atrium, is the main cause of severe mitral regurgitation and it often requires surgical or interventional correction. It mainly represents a typical adult disease with an average prevalence in industrialized countries ranging from 2 to 8%, but even the pediatric population may be affected showing specific features concerning both anatomy and treatment. Although its existence and clinical characteristics are known for several decades, every aspect of this pathological condition is in continuous evolution, being the subject of biologists’, cardiologists’ and surgeons’ active research. The aim of the present Research Topic is to address the MVP entity in its completeness, trying to describe all actual knowledge concerning molecular mechanisms, different clinical presentations (fibroelastic degeneration in elderly people or Barlow disease in young patients), diagnostic findings and tools (mainly represented by echocardiography and Nuclear Magnetic Resonance), their specific application to newly developed transcatheter and minimally invasive treatments, indications, surgical management and interventional strategies. For all these big chapters, special attention will be addressed to show temporal knowledge evolution and new elements acquisition, since the central message is that MVP is in flux and far from full comprehension.