Nonuniformity of mechanical performance is inherent to the multicellular nature and specific geometry and configuration of the ventricle of the heart. Although the concept of nonuniformity of the diseased heart is not new, ventricular function and the performance of the heart as a muscular pump cannot be understood unless nonuniform behavior is taken into account, even under normal conditions. Along with the loading conditions throughout the cardiac cycle and the time courses of activation and inactivation, the nonuniform behavior of load and of activation and inactivation in space and in time constitutes a third important determinant of mechanical performance and efficiency of the ventricle during both contraction and relaxation. Hence, a triad (load, activation-inactivation, nonuniformity) of controls regulates systolic function of the normal ventricle. In the diseased heart, even when loading and activation-inactivation are normal, the modulating role played by this nonuniformity can become imbalanced because of abnormal cavity size or shape or because of regional dysfunction. Such an imbalance would diminish external efficiency (the ratio of work performed to oxygen utilized) of the ventricle and result in incoordinate contraction and relaxation. These abnormalities, in turn, could exacerbate manifest cardiac failure.