--- - |2 Abstract Acute kidney injury (AKI) is frequently accompanied by activation of the sympathetic nervous system. This can be due to the presence of chronic diseases associated with sympathetic activation prior to AKI or induced by stressors that ultimately lead to AKI such as endotoxins and arterial hypotension in circulatory shock. Conversely, sympathetic activation may also result from acute renal injury. Focusing on studies in experimental renal ischemia and reperfusion (IR), this review summarizes the current knowledge on how the sympathetic nervous system is activated in IR‐induced AKI and on the consequences of sympathetic activation for the development of acute renal damage. Experimental studies show beneficial effects of sympathoinhibitory interventions on renal structure and function in response to IR. However, few clinical trials obtained in scenarios that correspond to experimental IR, namely major elective surgery, showed that perioperative treatment with centrally acting sympatholytics reduced the incidence of AKI. Apparently discrepant findings on how sympathetic activation influences renal responses to acute IR‐induced injury are discussed and future areas of research in this field identified. - 'Acta Physiologica, Volume 0, Issue ja, -Not available-. '