Acute kidney injury (AKI) is a common medical problem among critical patients. In current clinical practice, AKI is diagnosed by measuring serum creatinine concentration, which is an unreliable and delayed marker of the deterioration of kidney function. Its rise occurs when a significant amount of renal function has been lost. Many are the factors able to modify physiological levels, such as age, gender, ethnicity, dietary protein intake, muscle mass or metabolism, hydration status and drugs. Definitely, creatinine, as well as blood urea nitrogen (BUN) or urine markers of kidney injury (fractional excretion of sodium, urinary concentrating ability, casts), do not directly reflect cell injury, but rather the delayed functional consequences of the damage. Due to the lack of sensitive and specific biomarkers, the identification of early stages of AKI has been impossible but, recently, neutrophil gelatinase-associated lipocalin (NGAL) is emerging as a novel biomarker of AKI from several etiologies, such as cardiac surgery, contrast nephropathy, kidney transplantation and sepsis. This protein, produced in a number of human tissues and particularly in the distal nephron, has siderophore-chelating property and acts as an iron-trasporting shuttle. NGAL increases in both serum and urine 48 hours before the rise of creatinine, and shows a strong correlation with change in creatinine concentrations. An early diagnosis of AKI allows the early institution of therapeutic measures for the protection of renal function and improves the prognosis. This possibility is particularly important in the Emergency Department for the treatment of critical patients with potential nefrotoxic therapies. Use of NGAL as early marker of AKI in the Emergency Department is discussed.