The oxidation hypothesis of atherosclerosis suggests that oxidative modification of low-density lipoprotein (LDL) is a prerequisite for LDL atherogenicity. Recent studies demonstrate that upon oxidative modification, LDL becomes enriched with pathogen-associated molecular patterns recognized by natural (inborn) antibodies and innate immune receptors. This review focuses on recent findings showing that Toll-like receptors (TLRs)--which sense microbial pathogens and initiate immediate inflammatory responses--are potentially involved in the pathogenesis of atherosclerosis. In addition to the data that bacterial agonists of TLR4 and TLR2 accelerate atherosclerosis, new evidence suggests that minimally oxidized LDL and specific oxidized phospholipids signal via TLRs to induce cytoskeletal changes and inflammatory cytokine secretion by macrophages and endothelial cells. Identifying the signaling mechanisms by which oxidized LDL induces chronic inflammation in atherosclerotic lesions may lead to novel therapeutic targets for the treatment of atherosclerotic cardiovascular disease.