Neurogenic thoracic outlet syndrome (NTOS) is a relatively uncommon condition caused by compression and irritation of the brachial plexus nerve roots. The location of nerve compression may be within the scalene triangle at the level of the first rib or in the subcoracoid space beneath the pectoralis minor muscle tendon. NTOS most frequently occurs in relatively young, active, and otherwise healthy individuals, often in association with previous neck and/or upper extremity injury, and the symptoms may progress to cause substantial disability. Despite several decades of debate regarding proper diagnosis and optimal treatment, NTOS continues to be poorly understood and understudied. Thus, there is a tremendous need and opportunity for productive clinical research related to NTOS, particularly with increased emphasis on evidence-based medicine. In this chapter we outline some of the areas that appear to be most fruitful for investigation, and several strategies by which to help move forward our understanding and management of NTOS.