An increasing body of data has documented altered cytokine concentrations from Parkinson’s disease brains and its rodent models. These changes have been reported in the periphery as well as in the cerebrospinal fluid, where they may be released from a variety of cell types to possibly traffic to and from the brain. Brain resident macrophage, or microglia, is commonly implicated as the cell type contributing to cytokine elevations in the brain during disease. Beyond serving as biomarkers of disease, many studies indicate that the cytokines directly stimulate both neuroprotective and neurotoxic effects on dopaminergic neurons. In particular, rodent models of disease have allowed mechanistic testing of the correlative findings from human diseased brain to suggest that cytokines such as tumor necrosis factor-alpha and interleukin-1β have pleiotropic roles during disease that may vary based upon temporal concentrations and coincident stimulation.