Decisions about the best treatment options for patients with regional musculoskeletal pain must be made despite a lack of clear diagnostic criteria, an absence of robust outcome measures by which to assess response, and a paucity of evidence from high-quality randomized controlled trials. Although the randomized controlled trial is considered to be the 'gold standard' research design, it does not lend itself easily to the evaluation of all management strategies. This chapter explores these issues from a research perspective and reviews the various types of evidence available to help practitioners make informed decisions. The current evidence from systematic reviews in this area is summarized in the final part of the chapter.