Fibromyalgia (FM) is characterized by abnormal pain sensitivity in response to diverse stimuli as well as persistent widespread pain and other symptoms such as fatigue and sleep disturbance. Progress has been made in identifying factors that contribute to the etiopathogenesis of abnormal pain sensitivity, but there is no single model of pathophysiology or treatment of FM that has gained wide acceptance among health care professionals. We review the literature on the etiopathogenesis of abnormal pain sensitivity in FM and describe an explanatory model that serves as a source of testable hypotheses in our laboratory. This model posits that interactions of exogenous (eg, environmental stressors) and endogenous (eg, neuroendocrine dysfunction) abnormalities in genetically predisposed individuals lead to a final common pathway, ie, alterations in central nervous system function and neuropeptide production that underlie central sensitization and abnormal pain sensitivity. This model also suggests that efforts to develop and evaluate treatments for FM should focus on interventions with direct or indirect effects on central functions that influence pain sensitivity.