Acute kidney injury (AKI) is a syndrome characterized by a rise in creatinine or a decrease in urinary flow, according to the Kidney Disease Improving Global Outcomes (KDIGO) definition. It is diagnosed in 15% of inpatients and 50% of patients in the intensive care unit (ICU), and it is related to increased mortality. As part of a global effort aimed at the elimination of preventable deaths from AKI, there is a growing interest in identifying biomarkers that can be point-of-care and that are not influenced by the variability in patient characteristics in a relevant way. Neutrophil gelatinase-associated lipocalin (NGAL), particularly in its 25 kDa form, which is exclusively released by renal tubules, has emerged as a promising biomarker with potential use in the diagnosis of AKI in the critically ill, including its use in guiding the initiation and/or weaning of renal replacement therapy (RRT). The objective of this review is to summarize the current understanding of NGAL in acute settings, emphasizing biological and genomic insights.