<p>Hyperlactatemia is a frequent finding in critically ill patients and is traditionally interpreted as a marker of tissue hypoxia and anaerobic metabolism. However, in sepsis, septic shock, and other states of circulatory failure — including post-cardiac arrest syndrome — elevated lactate concentrations often occur despite preserved arterial oxygenation and adequate oxygen delivery. Increasing evidence indicates that lactate is a central metabolic intermediate whose circulating concentration reflects the balance between stress-induced production, cellular utilization, and organ clearance. While hepatic metabolism has long been considered the dominant pathway for lactate disposal, the kidneys — particularly proximal tubular cells — play a major and often underappreciated role in lactate utilization and clearance. Acute kidney injury (AKI), a common complication of sepsis, directly alters systemic lactate homeostasis. In this narrative review, we synthesize current knowledge on lactate biology in critical illness and examine the contribution of renal metabolism to hyperlactatemia in patients with sepsis-induced AKI. We propose that lactate should be interpreted as an integrated metabolic signal reflecting systemic stress and impaired clearance — rather than as a surrogate for hypoxia alone — with important implications for the management of septic AKI. The potential of urinary lactate as a marker of proximal tubular metabolic dysfunction and the emerging role of protein lactylation in modulating the inflammatory-to-reparative phenotypic transition are also discussed. </p>