Wall stress has been used as one of the parameters of myocardial mechanics. The present review focuses on recently developed data on ventricular wall stress, especially in relation to other newly developed areas in cardiology. In hypertensive hearts, there is a broad continuous spectrum in the structural and functional changes: those with low wall stress (inappropriate hypertrophy), those with normal wall stress (appropriate hypertrophy) and those with high wall stress (inadequate hypertrophy). Among them, the responses to neurohumoral stimuli are various, and their clinical features and courses also varied. These differences in wall stress among the different categories of hypertensive hearts may be caused by the variable influences of non-mechanical factors, such as molecular, metabolic and neurohumoral ones. Wall stress is an essential determinant of myocardial oxygen consumption, and is also an important determinant of the myocardial contractile state and diastolic function. In contrast to excitation-contraction coupling, contraction-excitation feedback has been studied, suggesting the importance of wall stress regulating electrical phenomena. The interrelationship between mechanical factors (including wall stress) and non-mechanical factors (including molecular, metabolic, neurohumoral and genetic ones) has been investigated intensively. In conclusion, wall stress (or force on the myocardial cell) may be a keystone in cardiology, relating to each of the cardiac phenomena. If wall stress deviates from the normal range, even with compensatory mechanisms, severe cardiac events occur. The compensatory mechanisms for wall stress may act as a risk factor on the heart, especially when the wall stress remains outside the normal range.