Human serum albumin (HSA) is a multifunctional plasma protein with a wide range of biochemical properties, including ligand-binding, antioxidant, and enzymatic activities. It is primarily synthesized in the liver and plays a key role in maintaining colloid osmotic pressure and vascular integrity. HSA is used clinically as a plasma expander, but recent studies suggest it does not provide a survival benefit over crystalloid solutions in critically ill patients. However, it has shown promise in certain conditions, such as liver disease and liver failure, where it may help reduce renal impairment and improve outcomes. HSA has a complex tertiary structure with multiple domains and flexible loops that allow it to bind a variety of substances, including fatty acids, drugs, and metal ions. It contains a cysteine residue (Cys-34) that can undergo redox modifications, influencing its antioxidant and anti-inflammatory properties. HSA can bind nitric oxide (NO), which may have protective effects, but excessive NO binding can lead to pro-oxidant effects. HSA also has the ability to bind and transport antioxidants such as bilirubin and NO, which may contribute to its protective role in oxidative stress. In liver disease, HSA is used for vascular volume maintenance and has been shown to improve outcomes in patients with cirrhosis and spontaneous bacterial peritonitis. More recently, HSA has been used in hemodialysis therapies, such as the molecular adsorbent recirculating system (MARS), which helps remove toxins and inflammatory mediators from the blood. HSA's ability to bind toxins, including bilirubin and copper ions, makes it a valuable component of such therapies. Despite its potential benefits, HSA has several contraindications, including known allergies and conditions where fluid overload could be harmful. It may also have pro-oxidant effects under certain conditions, and variations in HSA from different manufacturers may affect its efficacy and safety. The use of HSA in critically ill patients remains controversial, with some studies suggesting it may not provide a mortality advantage over crystalloid solutions. However, it may still be beneficial in specific clinical situations, such as in patients with cirrhosis or acute lung injury. Further research is needed to fully understand the role of HSA in critical care and liver disease.Human serum albumin (HSA) is a multifunctional plasma protein with a wide range of biochemical properties, including ligand-binding, antioxidant, and enzymatic activities. It is primarily synthesized in the liver and plays a key role in maintaining colloid osmotic pressure and vascular integrity. HSA is used clinically as a plasma expander, but recent studies suggest it does not provide a survival benefit over crystalloid solutions in critically ill patients. However, it has shown promise in certain conditions, such as liver disease and liver failure, where it may help reduce renal impairment and improve outcomes. HSA has a complex tertiary structure with multiple domains and flexible loops that allow it to bind a variety of substances, including fatty acids, drugs, and metal ions. It contains a cysteine residue (Cys-34) that can undergo redox modifications, influencing its antioxidant and anti-inflammatory properties. HSA can bind nitric oxide (NO), which may have protective effects, but excessive NO binding can lead to pro-oxidant effects. HSA also has the ability to bind and transport antioxidants such as bilirubin and NO, which may contribute to its protective role in oxidative stress. In liver disease, HSA is used for vascular volume maintenance and has been shown to improve outcomes in patients with cirrhosis and spontaneous bacterial peritonitis. More recently, HSA has been used in hemodialysis therapies, such as the molecular adsorbent recirculating system (MARS), which helps remove toxins and inflammatory mediators from the blood. HSA's ability to bind toxins, including bilirubin and copper ions, makes it a valuable component of such therapies. Despite its potential benefits, HSA has several contraindications, including known allergies and conditions where fluid overload could be harmful. It may also have pro-oxidant effects under certain conditions, and variations in HSA from different manufacturers may affect its efficacy and safety. The use of HSA in critically ill patients remains controversial, with some studies suggesting it may not provide a mortality advantage over crystalloid solutions. However, it may still be beneficial in specific clinical situations, such as in patients with cirrhosis or acute lung injury. Further research is needed to fully understand the role of HSA in critical care and liver disease.