Initially described as a hormone that regulates energy homeostasis, we now know that leptin is an integrative hormone that responds to and regulates various systems, in particular, the renal sympathetic nervous system. The rostral ventral lateral medulla (RVLM) contains neurons which evoke changes of arterial blood pressure by controlling the tonic and phasic activation of sympathetic activity. Thus, we sought to determine if leptin regulates blood pressure and renal sympathetic activity within the RVLM. Utilizing immunohistochemistry, we observed that neurons within the RVLM that receive sympathetic projections from the kidney express leptin receptors on them. We have also demonstrated that these neurons are responsive to low doses of leptin and evoke significant increases in blood pressure, renal sympathetic nerve activity and heart rate. Taken together, these data demonstrate that leptin can regulate blood pressure and renal sympathetic nerve activity within the RVLM.