Musculoskeletal soft tissue injuries such as Achilles tendinopathy and anterior cruciate ligament ruptures are common among elite athletes, recreational athletes and physically active individuals. The consequences of injury may be devastating and prevent the recreational or competitive athlete from reaching their potential or lead to a premature end to their careers. Although these injuries have been well described at a clinical level, the biological mechanisms causing these injuries are poorly understood. A further understanding of the biological mechanisms underlying the injury will assist the treatment and management of these injuries. In addition, understanding the biology is an important prerequisite in developing models that can be used to effectively identify risk, as well as, implement personalized prevention, treatment and rehabilitation programmes. Both intrinsic, including genetic variants, and extrinsic risk factors have nevertheless been implicated in the aetiology of these injuries. To date, several patents have been filed which involve the use of specific polymorphisms and regions within specific genes to be used in a genetic test for either tendon or ligament injury risk. The objective of this manuscript will be to review the evidence for the genetic predisposition to soft tissue injury, as well as the application of this data in the prevention, treatment and management of musculoskeletal soft tissue injuries.