Mitral valve prolapse is defined as abnormal bulging of the mitral valve leaflets into the left atrium during ventricular systole. Mitral valve prolapse is a common condition that is a risk factor for mitral regurgitation, congestive heart failure, arrhythmia, and endocarditis. Myxomatous degeneration is the most common cause of mitral prolapse in the United States and Europe, and progression of myxomatous mitral prolapse is the most common cause of mitral regurgitation that requires surgical treatment. Myxomatous degeneration appears to have genetic etiology. The genetics of myxomatous degeneration is complex and not fully worked out; it appears to be heterogeneous with multi-gene, multi-chromosomal autosomal dominance with incomplete penetrance. The molecular disorder of myxomatous degeneration appears to consist of a connective tissue disorder with altered extracellular matrix status and involves the action of matrix metalloproteinase, cysteine endoproteases, and tenomodulin. Treatment of mitral prolapse with regurgitation is complex, and the technological advances that are currently in development will be challenging and controversial.