Prostanoids are bioactive lipid mediators derived from arachidonic acid, a major precursor released from membrane phospholipids by phospholipase A2(PLA2) enzymes. Platelets primarily express Group IVA PLA2, which, upon activation, releases arachidonic acid for prostanoid biosynthesis. The cyclooxygenases (COX)-1 and -2 metabolize arachidonic acid to prostaglandin (PG)H2, a common precursor to various prostanoids, including thromboxane (Tx)A2, PGI2, PGD2, PGE2, and PGF2α. COX-1 operates in a constitutively inhibited state requiring high arachidonic acid concentrations, whereas COX-2 is more readily inducible by inflammatory stimuli. COX inhibition, particularly by nonsteroidal anti-inflammatory drugs (NSAIDs), significantly affects platelet function. Aspirin irreversibly acetylates COX-1, preventing TxA2 synthesis and thereby inhibiting platelet aggregation, which underlies its cardioprotective and bleeding effects. Other NSAIDs exhibit reversible COX inhibition, with varying degrees of interaction with aspirin. For example, ibuprofen and naproxen can interfere with aspirin’s irreversible COX-1 inhibition, potentially reducing its cardioprotective effects. TxA2, primarily synthesized in platelets, acts via the Tx receptor (TP), which has two isoforms (TPα and TPβ). TP receptor activation amplifies platelet aggregation and contributes to thrombus formation. Genetic mutations affecting TP signaling can result in mild bleeding disorders. TxA2 is rapidly hydrolyzed to TxB2, which is excreted in urine and serves as a biomarker of platelet activation. Prostaglandin D2(PGD2) is formed from PGH2 by PGD synthases and acts via DP1 and DP2 receptors. DP1, expressed in platelets, inhibits platelet activation via cyclic adenosine 3′,5′-monophosphate, cAMP, signaling. Prostacyclin (PGI2), a vasodilator and platelet inhibitor, is produced primarily in endothelial cells. The balance between PGI2 and TxA2 is critical for maintaining vascular homeostasis. Pharmacological modulation of these pathways has therapeutic implications in cardiovascular and inflammatory diseases.