Acute lung injury (ALI) and acute kidney injury (AKI) are complications often encountered in the setting of critical illness. Both forms of end-organ injury commonly occur in similar settings of systemic inflammatory response syndrome, shock, and evolving multiple organ dysfunction. Recent elucidation of the pathobiology of critical illness has led to a more basic mechanistic understanding of the complex interplay between injured organs in patients with multiple organ dysfunction syndrome; this has been aptly called ‘the slippery slope of critical illness’ [Kidney Int Suppl 1998;66:S25–S33]. Distant organ effects of apparently isolated injuries to the lungs, gut, and kidneys have all been discovered in recent years. In this article, we will review the harmful bidirectional interaction between ALI and AKI, which appears to be a common clinical syndrome with routine clinical implications. We will review the current understanding of lung-kidney interactions from both perspectives, including the renal effects of ALI and mechanical ventilation, and the pulmonary sequelae of AKI. In this review of the emerging evidence of deleterious bidirectional organ cross talk between lung and kidney, we will focus on the role of ventilator-induced kidney injury in the pathogenesis of AKI in patients with ALI.