Acute kidney injury (AKI) remains a major clinical challenge, especially in combination with acute lung injury (ALI). Clinical as well as experimental studies have provided evidence for clinically relevant kidney-lung interactions, ultimately leading to a drastic reduction in survival. The crosstalk between AKI and ALI is a consequence of both direct loss of normal organ function and inflammatory dysregulation resulting from each organ failure. Cellular (e.g. neutrophils) as well as soluble mediators (cytokines) contribute to the inflammatory dysregulation under these circumstances. Clinical interventions are currently limited to general, unspecific preventive or supportive measures. With respect to AKI, these strategies include adequate volume control, correction of acid-base/electrolyte abnormalities and elimination of uremic substances by renal replacement therapy. Lung protective ventilation, including low tidal volume ventilation, is a cornerstone in the management of ALI. This approach has been shown to attenuate both the direct mechanical effects of ventilation and the inflammatory response arising from ALI and mechanical ventilation, ultimately reducing the incidence of extrapulmonary organ failure. The fact that multiorgan failure is not only the sum of organ functions lost, but also includes inflammatory dysregulation together with a lack of treatment options greatly emphasizes the need for future research in this area.