The phospholipid/arachidonic acid second messenger system is a signaling system by which systemic regulators (hormones) and local mediators (tissue factors) control certain aspects of tissue metabolism. In vivo and in vitro evidence indicates that these effectors activate phospholipolytic enzymes in cellular membranes. The products of these enzymatic reactions (such as inositol phosphates or arachidonic acid metabolites) can serve as second messengers that can potentially influence glucose, lipid and protein metabolism at the cellular level. Alterations in this second messenger system could be involved in metabolic changes associated with some pathologic conditions as well as certain drug treatments, and thus, a better understanding of the system could reveal new possibilities for therapeutic interventions.