Chronic inflammation is associated with many neurodegenerative diseases, including multiple sclerosis, Parkinson's disease, and Alzheimer's disease. Increasing evidence that neuroinflammation contributes to disease severity has generated considerable interest in determining whether inhibition of inflammation pathways might be of therapeutic benefit. One potential avenue of intervention is provided by members of the nuclear receptor superfamily of ligand-dependent transcription factors that exert anti-inflammatory effects in many cell types. Here, we review recent studies providing insights into the distinct mechanisms that enable nuclear receptors to modulate immune responses, describe inflammatory components of neurodegenerative diseases, and discuss recent literature relevant to roles of nuclear receptors in influencing these processes.