The post-thrombotic syndrome (PTS) is an important chronic complication of deep vein thrombosis (DVT). The present review focuses on risk determinants of PTS after DVT and available means to prevent and treat PTS. More than one-third of patients with DVT will develop PTS, and 5% to 10% of patients develop severe PTS, which can manifest as venous ulcers. PTS has an adverse impact on quality of life as well as significant socioeconomic consequences. The main risk factors for PTS are persistent leg symptoms 1 month after acute DVT, anatomically extensive DVT, recurrent ipsilateral DVT, obesity, and older age. Subtherapeutic dosing of initial oral anticoagulation therapy for DVT treatment may also be linked to subsequent PTS. By preventing the initial DVT and DVT recurrence, primary and secondary prophylaxis of DVT will prevent cases of PTS. Daily use of elastic compression stockings for 2 years after proximal DVT appears to reduce the risk of PTS; however, uncertainty remains regarding optimal duration of use, optimal compression strength, and usefulness after distal DVT. The cornerstone of managing PTS is compression therapy, primarily using elastic compression stockings. Venoactive medications such as aescin and rutosides may provide short-term relief of PTS symptoms. Further studies to elucidate the pathophysiology of PTS, to identify clinical and biological risk factors, and to test new preventive and therapeutic approaches to PTS are needed.