Abstract <p>The esterase profile is a set of plasma proteins having esteraseactivity. Esterase profile can reflect various functional disordersin humans and animals and claims to be a universal marker for variousdiseases. Blood is a medium for numerous biologically active compounds,substrates, and metabolic products, and most adequately reflectschanges occurring in the body. The purpose of this review is togather information on current concepts of the structural, functional,and evolutionary features of esterases in human and animal blood.This article addresses the diversity of substrate specificity andcatalytic mechanisms of these enzymes, discusses the evolutionary originsof esterases and their adaptation to performing specific physiologicalfunctions. In conclusion, the significance of esterases as diagnosticmarkers for conditions, such as organophosphate poisoning, cardiovasculardiseases, and Alzheimer’s disease, is emphasized. A deeper insightinto the structure–function relationship of esterases will opennew prospects for their therapeutic application and improvementof diagnostic strategies in medicine.</p>