Fibromyalgia (FM) is a condition characterized by chronic widespread pain, which has traditionally been considered psychogenic in nature due to lack of known underlying organic pathophysiology. In more recent years, inflammation of the nervous system has become increasingly recognized as a sign of neuropsychiatric conditions, and this association may enhance our knowledge of conditions such as FM. Emerging evidence has suggested inflammation, particularly neuroinflammation, as a potential contributor underlying the etiology of FM. Studies have searched for linked biomarkers with mixed results, though the literature is beginning to point to increased systemic levels of pro-inflammatory cytokines such as IL-6 and IL-8 in patients with FM relative to healthy controls. A multicenter imaging study has also reported results suggestive of microglial activation related to the presence of FM. Given the consistency in neuroinflammatory effects implicated in “sickness behavior” characteristic of chronic systemic inflammatory conditions such as cancer or rheumatic diseases, therein springs the hypothesis for a connection between FM and neuroinflammation as discussed in this chapter.