Almost any injury to the brain may initiate disturbances in local and systemic coagulation. This statement is particularly true for subarachnoid hemorrhage, traumatic brain injuries, and cranial and spinal dural arteriovenous fistulae. The pathogenesis of coagulative disorders is highlighted from both a genetic and a structural biology perspective, along with a discussion of predictive biomarkers and clinical risk factors to guide the selection of eligible patients for primary prevention. This comprehensive review allows a better understanding of the coagulative disorders affecting patients harboring CNS diseases and accordingly offers new insights into their pharmacological and surgical treatment.