Inherited and acquired thrombophilic disorders have recently been associated with cerebral palsy (CP) and complications in pregnancy. Thrombophilic disorders are not diseases per se, but are recognized risk factors for a variety of diseases across all ages, including atherosclerosis, cerebral infarction, inflammatory bowel disease, Legg–Perthes disease, deep venous thromboses, and preeclampsia. In healthy individuals, the balance between procoagulant and anticoagulant mechanisms is exquisitely regulated, protecting against both excessive bleeding and excessive clotting (thrombophilia). This annotation is intended to be a broad overview of thrombophilia, with special attention to the factor-V Leiden (fVL) mutation, an autosomal dominant point mutation resulting in resistance to activated protein C (APC). This thrombophilic disorder has wide clinical implications for the management of carrier women and their offspring, as illustrated by the accompanying case report.