Acute kidney injury (AKI) is a significant independent risk factor for morbidity and mortality. In the last ten years a large number of publications have highlighted the limitations of traditional approaches and the inadequacies of conventional biomarkers to diagnose and monitor renal insufficiency in the acute setting. A great effort was directed not only to the discovery and validation of new biomarkers aimed to detect AKI more accurately but also to standardise the definition of AKI. Despite the advances in both areas, biomarkers have not yet entered into routine clinical practice and the definition of this syndrome has many areas of uncertainty. This review will discuss the controversies in diagnosis and the potential of novel biomarkers to improve the definition of the syndrome.