The inflammatory response mounted by the immune system is a protective process necessary for survival following exposure to insults. However, it must be tightly regulated to maximize efficient elimination of pathogens and to minimize collateral damage to the host. Failure to maintain balance and resolve an inflammatory response can result in chronic systemic inflammation (CSI). CSI has been identified as a key factor in the pathogenesis of many diseases including neurodegenerative diseases (NDs). This review covers the growing relationship between CSI and NDs with a particular emphasis on Parkinson's disease (PD). Furthermore, we discuss the role of an important negative regulator of inflammatory responses: Regulator of G-protein Signaling-10 (RGS10), within the context of CSI and PD.