Venous thromboembolism is a common disease that causes significant morbidity and mortality. In recent years, the ability to diagnose inherited genetic defects and common acquired conditions predisposing to thrombosis has greatly increased. Venous thromboembolism is now understood to be a complex interaction of genetic and environmental factors leading to thrombosis. Integrating the various factors to individually assess thrombotic risk still poses a challenging clinical problem that will likely become easier as more data accumulate. As the ability to accurately assess risk increases, the data can then be translated into tailored treatment regimens. Until then, only general guidelines regarding evaluation and management are available. In the future, it is likely that other prothrombotic conditions will be elucidated, adding to the pool of data.