Acute kidney injury is a common condition in hospitalized patients with significant associated morbidity and mortality. Although impressive progress has been made in the understanding of the molecular and biochemical mechanisms of kidney injury, the ability to effectively treat and thus impact on the outcomes of acute kidney injury has been disappointing. One of the major reasons for this has been the reliance on current measures of renal dysfunction, such as serum creatinine and blood urea nitrogen, which are insensitive to small changes in renal function and subtle signs of kidney injury. This insensitivity of commonly used biomarkers of renal dysfunction not only prevents timely diagnosis and estimation of injury severity, but also delays administration of putative therapeutic agents. A number of serum and urinary proteins have been identified that may herald acute kidney injury prior to a rise in serum creatinine. Further characterization of these candidate biomarkers will clarify their utility and define new diagnostic and prognostic paradigms for acute kidney injury, facilitate clinical trials and lead to novel effective therapies.