AbstractObjectivesPerceptions that formulations of human albumin solution have not evolved and are interchangeable need to be reconsidered amid renewed appreciation of this therapy in its current uses, and in potential new uses. Initially indicated for volume expansion in severely ill or trauma patients, human albumin solution has been established in a broadening array of clinical applications as understanding of its structure–function relationships has deepened. This article reviews the clinical roles of human albumin solution, the evolution of manufacturing processes and the growing interest in the use of albumin as a therapeutic agent in an expanding range of clinical scenarios.MethodsLiterature searching was conducted through PubMed, bibliographies of prior publications specific to human albumin solution and ClinicalTrials.gov. This review includes multidisciplinary perspectives on the chemistry, physiology, extraction, processing, formulation and clinical applications of human albumin based on the published literature, authors’ professional experience and product quality-assurance data.Key findingsCurrent formulations of human albumin solution vary in composition, including the use of chemical stabilizers and concentrations of key electrolytes, especially sodium and chloride. Through innovations in manufacturing processes since the 1990s, Zenalb 20 is defined by its high albumin purity, use of a single stabilizer and electrolyte concentrations that are substantially lower than in normal human plasma. The clinical relevance of these features may increase as the use of human serum albumin continues to expand in patient populations receiving multiple medications and fluids, for whom electrolyte balance is crucial.ConclusionAs a low electrolyte formulation, Zenalb 20 provides a clinical option to increase oncotic pressure when a colloid is needed without worsening pathological hypernatraemia, hyperchloraemia and hyperkalaemia.