Chronic dysregulation of early proatherogenic inflammatory pathways may lead to the activation of innate and adaptive immune responses that affect the endothelium, platelets, and arterial wall. A central outcome from the activation of these inflammatory pathways is the oxidative modification of lipoproteins that trigger mononuclear cell activation, cytokine production, and excessive intracellular accumulation of lipids within atherosclerotic lesions. Innate immunity represents an early defense against pathogens and metabolic or endogenous danger molecules. Similar to the adaptive immunity, a dysregulated innate immunity can cause tissue damage, inflammation, and disease. Nucleotide-binding leucine-rich receptor (NLRs) are a family of cytoplasmic receptors for endogenous danger molecules. Inflammasomes are multimolecular complexes of pyrin-containing NLRs (NLRPs) that regulate proinflammatory caspases-1 and interleukin 1 (IL-1) cytokines in response to various stimuli. Modified cholesterol, oxidation-derived by-products such as oxidized low-density lipoprotein and reactive oxygen species have been described as endogenous signals capable of activating NLRP inflammasomes. Inflammasome-induced IL-1β responses may represent an early mechanism in atherosclerosis.