Inflammation is a central component of several chronic human diseases, including atherosclerosis and type 2 diabetes. Several nuclear receptors repress inflammatory responses, but their molecular mechanisms remain poorly understood. The nuclear receptor superfamily is composed of transcription factors that have emerged as key regulators of inflammation and lipid homeostasis. These include the glucocorticoid receptor, which inhibits inflammatory programs of gene expression in response to natural corticosteroids and synthetic anti-inflammatory ligands such as dexamethasone. In addition, peroxisome proliferator-activated receptors and liver X receptors, in response to endogenous eicosanoids and oxysterols, respectively, modulate transcriptional pathways involved in inflammatory responses and lipid homeostasis.