Hemostasis is the ability of the body to control blood loss following vascular injury. The process is composed of a complex array of pathways made up of the coagulation and fibrinolytic systems that allow the fluid blood to clot after injury and then the subsequent breakdown of the clot, permitting repair of the injured tissue. Studies to date have shown exercise to be a stimulating factor in both the coagulation and fibrinolytic pathways. Additionally, air travel has been shown to be a risk factor for thrombosis. However, few studies have examined the combination of exercise and air travel on hemostasis, despite documented evidence of venous thrombotic episodes in the sports and endurance (marathon/triathlon) communities. This review summarizes and analyzes the literature with regard to (1) acute and chronic exercise, (2) air travel, and (3) exercise and air travel. In addition, the review examines confounding variables that may contribute to coagulation and strategies to prevent blood clot formation after exercise and during air travel.