Despite considerable progress in the diagnosis and treatment of deep-vein thrombosis (DVT) of the lower extremities, one of every 2-3 patients will develop within 2 years post-thrombotic sequelae, which are severe in approximately 10% of cases and produce considerable socio-economic consequences. Among factors potentially related to the development of the post-thrombotic syndrome (PTS) are older age, obesity, a history of previous ipsilateral DVT, iliac-femoral location of the current thrombosis, failure to promptly recover from the acute symptoms and insufficient quality of oral anticoagulant therapy. Based on recent findings, the lack of vein recanalization within the first 6 months after DVT appears to be an important predictor of PTS, while the role of venous reflux is controversial. According to the results of recent clinical studies, the prompt administration of adequate compression elastic stockings in patients with symptomatic DVT has the potential to halve the frequency of PTS, and when carefully supervised and instructed to wear proper elastic stockings, more than 50% of patients have the potential to either remain stable or improve during long-term follow-up. Nevertheless, due to limitations in current therapies, the management of PTS is demanding and often frustrating. Further research is required to optimize the prevention and management of this common and burdensome complication of DVT.