In the last 10–15 years, interest in the physiological role of P2 receptors has grown rapidly. Cellular, tissue, and organ responses to P2 receptor activation have been described in numerous in vivo and in vitro models. The purpose of this review is to provide an update of the recent advances made in determining the involvement of P2 receptors in the control of renal hemodynamics and the renal microcirculation. Special attention will be paid to work published in the last 5–6 years directed at understanding the role of P2 receptors in the physiological control of renal microvascular function. Several investigators have begun to evaluate the effects of P2 receptor activation on renal microvascular function across several species. In vivo and in vitro evidence consistently supports the hypothesis that P2 receptor activation by locally released extracellular nucleotides influences microvascular function. Extracellular nucleotides selectively influence preglomerular resistance without having an effect on postglomerular tone. P2 receptor inactivation blocks autoregulatory behavior whereas responsiveness to other vasoconstrictor agonists is retained. P2 receptor stimulation activates multiple intracellular signal transduction pathways in preglomerular smooth muscle cells and mesangial cells. Renal microvascular cells and mesangial cells express multiple subtypes of P2 receptors; however, the specific role each plays in regulating vascular and mesangial cell function remains unclear. Accordingly, the results of studies performed to date provide strong support for the hypothesis that P2 receptors are important contributors to the physiological regulation of renal microvascular and/or glomerular function.