It is estimated that 40 million people in the USA have hypertension, 14 million are diabetic and 4 million suffer congestive heart failure. Since all three conditions are age-related, as the longevity in industrialized societies continues to improve, the overall burden of congestive heart failure, hypertension and diabetes will increase. These major diseases of civilization are characteristically associated with an increased autonomic cardiovascular drive. In our terminology the output that emanates from the central nervous system via sympathetic and parasympathetic efferents is referred to as "tone". The overall "drive" depends on the balance between inhibitory (parasympathetic) and excitatory (sympathetic) tone and the organ's responsiveness to that tone. The responsiveness, in turn, depends on the receptors' properties as well as on the intrinsic functional or anatomic properties of the responding organs. These components can change independently. For example, in the course of hypertension the alpha-adrenergic responsiveness increases whereas the beta-adrenergic responses are down-regulated. Another example is: plasma noradrenaline and sympathetic tone are increased in elderly subjects but their circulation does not show any tell-tale response of increased sympathetic tone, presumably because the responses to sympathetic tone decrease with aging. These complex interactions between the autonomic tone and organ responsiveness determine to a great extent the overall clinical impact of the autonomic abnormality in hypertension, non-insulin-dependent diabetes mellitus and in congestive heart failure. The major thesis of this review is that, whether primary or secondary, whether easily discerned or hidden, an enhanced autonomic drive, independent of the underlying condition, greatly increases the risk of poor cardiovascular outcomes. It follows that targeting the underlying autonomic imbalance in congestive heart failure, hypertension and diabetes may not only be pathophysiologically sound but such an approach may also lead to better outcomes.