Fibromyalgia syndrome (FMS) is now understood as a chronic pain syndrome, and recent evidence indicates it is not a pure psychosomatic disorder. We review the current knowledge in FMS pain pathways, focusing on the central system sensitization phenomenon and the abnormalities in the inhibitory pain systems. Chronic headache is one of the most common symptoms in FMS, and better knowledge of their common pathophysiologic features can help us understand both conditions better. These features include the nerve growth factor actions and failure of the endocannabinoid system. In addition, we review new immunological aspects of FMS, both in their humoral (autoantibodies, antipolymer antibodies) and cytokine (interleukin-2) aspects.