Glucocorticoids (GCs) are hormones released during the stress response that are well known for their immunosuppressive and anti-inflammatory properties; however, recent advances have uncovered situations wherein they have effects in the opposite direction. The CNS is a particularly interesting example, both because of its unique immune environment, and because GCs affect immune responses differently in different brain regions. In this minireview we discuss the contexts wherein GCs increase CNS inflammation and point out directions for future investigation.