The goal of treating deep vein thrombosis (DVT) is to prevent pulmonary embolism (PE) and death from PE, reduce the risk of recurrent DVT, and avoid postthrombotic morbidity. To manage DVT optimally, an understanding of its natural history is important. It is helpful to conceptualize venous thrombosis as an imbalance of the patient’s coagulation system with the fibrinolytic system at the time of the acute event and over the long term. Anticoagulation is designed to shift this imbalance toward the patient’s endogenous fibrinolytic system to reduce endovenous coagulation. If the patient’s fibrinolytic system is capable of resolving the majority of the acute clot, postthrombotic morbidity will be reduced and potentially avoided. However, if the effectiveness of the fibrinolytic system is minimal or if thrombus extension or rethrombosis occurs, the likelihood of additional venous thromboembolic complications and postthrombotic morbidity is high.