Numerous animal studies have demonstrated that pyruvate holds superior biological properties relative to anions in traditional solutions in fluid therapy for critical illness. The beneficial characteristics include increase of hypoxia tolerance, anti-oxidative and inflammatory effects, correction of hypoxic lactic acidosis and protection of mitochondrial function. Therefore, pyruvate-enriched solutions are potentially suitable for fluids resuscitation in critical care patients to prevent "resuscitation injury" induced by traditional fluid. For example, 0.9% sodium chloride solution commonly induces hyperchloremic acidosis, sodium lactate solution may inhibit glycolysis and both can lead to systemic inflammatory reactions in clinical fluid therapy. Pyruvate in fluid therapy is not only a volume expander, but also a therapeutic agent in prevention of multi-organ, particularly intestinal barrier, dysfunction. Thus, pyruvate appears its superiority in fluid therapy. Many animal experiments in vivo and preliminary clinical trials have demonstrated that pyruvate protects organ function and improves oxidative metabolism, specially corrects hypoxic lactic acidosis. It protects glycolytic metabolism under hypoxia, even anoxia, through lactate dehydrogenase reaction and stimulation of hypoxia inducible factor-1α; it also promotes glucose oxidative metabolism under hypoxia due to its restoration of inhibited activity of pyruvate dehydrogenase, resulting in improvement of lactic clearance. The pyruvate favorable function can be achieved by intravenous, peritoneal or oral administrations in fluid therapy of fatal shock animals. These aspects were mainly reviewed in this paper. In addition, pyruvate prevents organ complications associated with diabetes, such as retinopathy, and shows anti-cancer property under some conditions. Current findings strongly demonstrate its huge potential values and promising prospects in clinical application. Further concerns and investigations are warranted.