The diagnosis of thoracic outlet syndrome (TOS) has long been a controversial and challenging one. Despite common presentations with pain in the neck and upper extremity, there are a host of presenting patterns that can vary within and between the subdivisions of neurogenic, venous, and arterial TOS. Furthermore, there is a plethora of differential diagnoses, from peripheral compressive neuropathies, to intrinsic shoulder pathologies, to pathologies at the cervical spine. Depending on the subdivision of TOS suspected, diagnostic investigations are currently of varying importance, necessitating high dependence on good history taking and clinical examination. Investigations may add weight to a diagnosis suspected on clinical grounds and suggest an optimal management strategy, but in this changing field new developments may alter the role that diagnostic investigations play. In this article, we set out to summarise the diagnostic approach in cases of suspected TOS, including the importance of history taking, clinical examination, and the role of investigations at present, and highlight the developments in this field with respect to all subtypes. In the future, we hope that novel diagnostics may be able to stratify patients according to the exact compressive mechanism and thereby suggest more specific treatments and interventions.