Cyclooxygenase (COX) catalyses the first committed step in the biosynthesis of a large family of arachidonic acid metabolites comprising of prostaglandins (PGs), prostacyclin, and thromboxanes (TXs), which are collectively known as prostanoid. Three isoforms, COX-1, COX-2 and COX-3, have been identified. COX-1 is the constitutive form of cyclooxygenase and performs a housekeeping function in regulating normal activities.COX-2 is the inducible isoform, rapidly expressed in several cell types in response to growth factors, cytokines and pro-inflammatory molecules. COX-2 expression in the brain has been associated with pro-inflammatory activities and is thought to be instrumental in the neurodegenerative processes of several acute and chronic diseases. Also, all the isoforms of COX enzymes are major targets of non-steroid anti-inflammatory drugs (NSAIDs). Many studies indicate the involvement of COX-2 in the information process and physiological mechanism of Memory. For instance, intrahippocampal infusion of celecoxib, a COX-2- specific inhibitor, impaired spatial Memory acquisition and Memory retention (Sharifzadeh et al. 2005). Some reports provide evidence in support of the interacting effects of nicotine and the COX-2 pathway in the brain. There is also some evidence of cross talks between cAMP/PKA pathway and COX cascades; one of the important interactions reported was between PKA and COX products pathways. Activation of PKA may create long-term Memory by regulating gene expression. PKA can modify transcription by phosphorylating several different transcription factors, one of which is the cAMP response element binding protein (CREB). The aim of this review is to clarify the role of COX isozymes in Memory disorders.