Mitral regurgitation is a growing cardiac issue and is associated with increase morbidity and mortality. This condition represents a very heterogenous disease, which can by a primary defect of mitral valve apparatus that through volume overload can lead to left ventricular dysfunction and heart failure, or can be secondary to left ventricular remodeling and dysfunction due to an ischemic or non-ischemic cause. Definition of mechanism and etiology of MR and correct grading are essential for management strategy and timing. Extended Heart Team and multimodality imagistic techniques and multi-parametric approach of patients with mitral regurgitation and heart failure are, therefore, mandatory. When indicated, mitral surgery is the treatment of choice in primary mitral regurgitation and with heart failure patients, with repair whenever is possible, meanwhile, the initial cornerstone of management is optimized guideline-directed medical treatment, with surgical or percutaneous trans-catheter intervention as second line of therapy in patients with secondary mitral regurgitation. Our review will discuss aspects regarding the anatomy and function of the complex mitral apparatus, mechanisms, etiologies and pathophysiology of mitral regurgitation and heart failure, different diagnostic tools and management strategies and timing in both primary and secondary mitral regurgitation.