Plasma protein therapies have been sheltered historically from the scrutiny of evidence-based medicine. Thus, a number of albumin solutions became part of the established therapeutic armamentarium with a very modest evidence base. As evidence-based medicine has turned its focus on plasma protein therapies, albumin's appropriate use has become increasingly questioned. Concurrently, interest in other colloid plasma expanders has increased as efforts to address their side-effects have resulted in new products.

The decade-old meta-analysis from the Cochrane collaboration linking albumin with increased mortality, although currently disproven, has resulted in ongoing scrutiny of albumin's safety and has led to a large randomized clinical trial which, while demonstrating equivalent safety with saline, has also shown equivalent mortality in the patient population assessed. Albumin's manufacture yields products which vary between different brands, as well as occasionally between batches from the same brand. These changes affect albumin's physiologic properties and may contribute to the different therapeutic effects observed in clinical practice. More clinical investigations of albumin's therapeutic role are needed before its unique biological features can be shown to result in therapeutically useful drugs.