The matching of capillary blood flow to metabolic rate of the cells within organs and tissues is a critical microvascular function which ensures appropriate delivery of hormones and nutrients, and the removal of waste products. This relationship is particularly important in tissues where local metabolism, and hence capillary blood flow, must be regulated to avoid a mismatch between nutrient demand and supply that would compromise normal function. The consequences of a mismatch in microvascular blood flow and metabolism are acutely apparent in the brain and heart, where a sudden cessation of blood flow, for example following an embolism, acutely manifests as stroke or myocardial infarction. Even in more resilient tissues such as skeletal muscle, a short-term mismatch reduces muscle performance and exercise tolerance, and can cause intermittent claudication. In the longer-term, a microvascular-metabolic mismatch in skeletal muscle reduces insulin-mediated muscle glucose uptake, leading to disturbances in whole-body metabolic homeostasis. While the notion that capillary blood flow is fine-tuned to meet cellular metabolism is well accepted, the mechanisms that control this function and where and how different parts of the vascular tree contribute to capillary blood flow regulation remain poorly understood. Here, we discuss the emerging evidence implicating pericytes, mural cells that surround capillaries, as key mediators that match tissue metabolic demand with adequate capillary blood flow in a number of organs, including skeletal muscle.