P2 receptors are expressed by renal vascular, glomerular, mesangial and tubular epithelial cells, suggesting that extracellular ATP serves a diverse array of physiological roles in regulating renal hemodynamic and tubular function. Evidence indicates that ATP, or its analogues, alter renal vascular resistance and renal blood flow significantly in vitro and in vivo. This review will focus on the recent evidence that supports extracellular ATP as an important regulator of renal microvascular function. The vascular actions of ATP involve the activation of P2X receptors to regulate renal vascular function, renal blood flow and also to mediate renal autoregulatory behavior. The review will also consider the implication that renal microvascular dysfunction in disease is related to P2 receptor dysfunction and we highlight some important issues and challenges that require further attention.