Acute kidney injury is an increasingly common and potentially catastrophic complication in hospitalized patients. Early observational studies from the 1980s and 1990s established the general epidemiologic features of acute kidney injury: the incidence, prognostic significance, and predisposing medical and surgical conditions. Recent multicenter observational cohorts and administrative databases have enhanced our understanding of the overall disease burden of acute kidney injury and trends in its epidemiology. An increasing number of clinical studies focusing on specific types of acute kidney injury (e.g., in the setting of intravenous contrast, sepsis, and major surgery) have provided further details into this heterogeneous syndrome. Despite our sophisticated understanding of the epidemiology and pathobiology of acute kidney injury, current prevention strategies are inadequate and current treatment options outside of renal replacement therapy are nonexistent. This failure to innovate may be due in part to a diagnostic approach that has stagnated for decades and continues to rely on markers of glomerular filtration (blood urea nitrogen and creatinine) that are neither sensitive nor specific. There has been increasing interest in the identification and validation of novel biomarkers of acute kidney injury that may permit earlier and more accurate diagnosis. This review summarizes the major epidemiologic studies of acute kidney injury and efforts to modernize the approach to its diagnosis.