Multivalvular heart disease (MVD) implies the presence of concomitant valvular lesions on two or more heart valves. This condition has become common in the few last years, mostly due to population aging. Every combination of valvular lesions uniquely redefines the hemodynamics of a patient. Over time, this may lead to alterations in left ventricle (LV) dimensions, shape and, eventually, function. Since most of the echocardiographic parameters routinely used in the valvular assessment have been developed in the context of single valve disease and are frequently flow- and load-dependent, their indiscriminate use in the context of MVD can potentially lead to errors in judging lesion severity. Moreover, the combination of non-severe lesions may still cause severe hemodynamic consequences, and thereby systolic dysfunction. This review aims to discuss the most frequent combinations of MVD and their echocardiographic caveats, while addressing the opportunities for a multimodality assessment to achieve a better understanding and treatment of these patients.