Phospholipase A2 (PLA2) is an enzyme that catalyzes the hydrolysis of membrane phospholipids. This article reviews the source and structure of PLA2, the involvement of the enzyme in various biological and pathological phenomena, and the usefulness of PLA2 assays in laboratory diagnostics. Of particular importance is the role of PLA2 in the cellular production of mediators of inflammatory response to various stimuli. Assays for PLA2 activity and mass concentration are discussed, and the results of enzyme determinations in plasma from patients with different pathological conditions are presented. The determination of activity and mass concentration in plasma is particularly useful in the diagnosis and prognosis of pancreatitis, multiple organ failure, septic shock, and rheumatoid arthritis. A very important result is the demonstration that PLA2 is an acute phase protein, like CRP. Indeed, there is a close correlation between PLA2 mass concentration and CRP levels in several pathological conditions. Although the determination of C-reactive protein is much easier to perform and is routinely carried out in most clinical laboratories, the assessment of PLA2 activity or mass concentration has to be considered as a reliable approach to obtain a deeper understanding of some pathological conditions and may offer additional information concerning the prognosis of several disorders.