Deep vein thrombosis (DVT) is a common clinical condition. While most patients will improve dramatically with appropriate acute and long-term treatment, up to half will develop chronic symptoms called the post-thrombotic syndrome (PTS). PTS can range from mild cosmetic changes to significant debilitating symptoms including leg pain, significant edema, and venous ulceration. Despite its high prevalence, prevention and treatment options remain limited. In this chapter, we will review the known pathophysiology and natural history of PTS as well as discuss available prevention and management strategies.