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Atherosclerosis is a chronic disease of the vasculature that is influenced by multiple factors that involve a complex interplay between some components of the blood and the arterial wall. Inflammation and oxidative stress have key roles in atherogenesis. The production of F₂-isoprostanes (F₂-IPs), thromboxane A₂ (TxA₂) and prostacyclin (PGI₂) increases in atherosclerosis, and recent studies show that pharmacological modulation of their biosynthesis and biological activities are important therapeutic targets for managing atherosclerosis. In this review, we highlight recent breakthroughs in the roles of F₂-IPs, TxA₂ and PGI₂ in atherogenesis, and identify pertinent therapeutic targets.