This communication will discuss the spasm of resistance vessel concept of ischemic heart disease and other ischemic diseases, and will focus on ischemic heart disease. The hypothesis is regarded as a separate model or paradigm, and is based on the principle that spasm of resistance vessels directly induces symptoms in these conditions. Resistance vessels help maintain vascular homeostasis through autoregulatory mechanisms, and spasm of resistance vessels is considered to represent 'inappropriate' activation of these mechanisms by disease states, which are equated with risk factors. For ischemic heart disease, the most important risk factor is stenotic coronary artery disease, and the concept asserts that severe ischemia secondary to coronary artery disease causes sufficient tissue injury to incite injury-spasm of resistance vessels. While it is universally accepted that occlusions of epicardial arteries by stenotic coronary artery disease, spasm, and thromboses directly induce clinical symptoms, the hypothesis suggests that these occlusions have other roles. The concept accepts all current treatments of ischemic heart disease, but as this disorder is viewed differently, a significantly different direction of research is proposed for improving its treatment and prevention.