Dopamine receptors have been identified in a number of organs and tissues, which include the central and peripheral nervous systems, various vascular beds, the heart, the gastrointestinal tract, and the kidney. Dopamine receptors are classified into D1- and D2-like subtypes based on their structure and pharmacology; during conditions of moderate sodium balance, more than 50% of renal sodium excretion is regulated by D1-like receptors. Most of the knowledge on the actions of dopamine has been focused on the D1 dopamine receptor. The D5 dopamine receptor also belongs to the D1-like receptor subfamily. Disruption of the D5 receptor results in hypertension. However, unlike the D1 receptor, the hypertension in D5 receptor null mice is caused by the increased activity of the sympathetic nervous system, apparently due to activation of oxytocin, V1 vasopressin, and non-NMDA receptors in the central nervous system. In this paper, we review the physiological action of D5 receptor on the central and peripheral nervous systems, and discuss the possible mechanisms by which hypertension develops when the D5 receptor function is perturbed.