Chronic diffuse pain and hyperalgesia are two cardinal features of pain in fibromyalgia syndrome (FMS). Advancement in understanding the pathophysiology and treatment efficacy often depends on pain that is defined and measured. Pain is a subjective phenomenon that we can measure only by indirect methods. In this article, we provide methodological guidelines for pain assessment and review recent developments in understanding pain mechanisms and evaluating treatments in FMS. Finally, we demonstrate the heterogeneity of the FMS population and suggest the need for matching treatments to patient characteristics in order to improve clinical outcomes.