Conditions affecting kidney structure and function can be considered acute or chronic, depending on their duration. Acute kidney injury (AKI) is one of a number of acute kidney diseases and consists of an abrupt decline in kidney function after an injury leading to functional and structural changes. The widespread availability of enabling technologies has accelerated the rate of novel biomarker discovery for kidney injury. The introduction of novel biomarkers in clinical practice will lead to better preventative and therapeutic interventions and to improve outcomes of critically ill patients. A number of biomarkers of functional change and cellular damage are under evaluation for early diagnosis, risk assessment, and prognosis of AKI. Neutrophil gelatinase-associated lipocalin (NGAL) has emerged as the most promising biomarker of kidney injury; this protein can be measured by commercially available methods in whole blood, plasma, serum, and urine. Concomitantly, metabolomics appears to be a snapshot of the chemical fingerprints identifying specific cellular processes. In this paper, we describe the role of NGAL for managing AKI and the potential benefits deriving from the combined clinical use of urine NGAL and metabolomics in kidney disease.