Protection of renal function and prevention of acute renal failure (ARF) are important goals of resuscitation in critically ill patients. Beyond fluid resuscitation and avoidance of nephrotoxins, little is known about how such prevention can be achieved. Vasoactive drugs are often administered to improve either cardiac output or mean arterial pressure in the hope that renal blood flow will also be improved and, thereby, renal protection achieved. Some of these drugs (especially low-dose dopamine) have even been proposed to have a specific beneficial effect on renal blood flow. However, when all studies dealing with vasoactive drugs and their effects on the kidney are reviewed, it is clear that none have been demonstrated to achieve clinically important benefits in terms of renal protection. It is also clear that, with the exception of low-dose dopamine, there have been no randomized controlled trials of sufficient statistical power to detect differences in clinically meaningful outcomes. In the absence of such data, all that is available is based on limited physiological gains (changes in renal blood flow or urine output) with one or another drug in one or another subpopulation of patients. Furthermore, given our lack of understanding of the pathogenesis of ARF, it is unclear whether haemodynamic manipulation is an appropriate avenue to achieve renal protection. There is a great need for large randomized controlled trials to test the clinical, instead of physiological, effects of vasoactive drugs in critical illness.