Background Paget-Schroetter Syndrome (PSS) is an uncommon disorder involving thrombosis of the subclavian vein, often caused by repetitive overuse or compression by the surrounding anatomical structures. Optimal management of PSS is a subject of debate, but current trends suggest that a hybrid approach employing endovascular intervention and open decompression may yield the best clinical results. This original article examines the roles played by endovascular thrombolysis, surgical decompression, and postoperative secondary intervention in the management of PSS. Methods Current literature on the management of PSS was reviewed and evaluated to ascertain what strategy of intervention would be optimal. In addition, clinical data from the University Hospital of Wales on the clinical outcomes in PSS patients undergoing different surgical approaches for anatomical decompression are included. Results Evaluation of data from the included series and available literature seems to indicate that endovascular thrombolytic devices such as the AngioJet or mechanical thrombectomy offer superior results than traditional catheter-directed thrombolysis. In addition, adjunctive procedures such as superior vena cava filters and venous angioplasty or bypass may augment maintenance of the subclavian vein lumen. Nonetheless, the subclavian vein must still be relieved of pressure from surrounding structures for treatment to be successful. Conclusions A hybrid approach to the management of PSS, encompassing endovascular and surgical interventions could possibly offer optimal clinical outcomes as both intrinsic lesions and extrinsic compression of the subclavian vein are resolved. This article recommends prospective research to determine the ideal endovascular treatment, and best surgical approach for decompression.