Despite a plethora of guidelines for return to play following mild head injury, a discussion of when and if an athlete should be allowed to participate in contact or collision sports if he or she sustains a structural brain lesion or after a head injury requiring craniotomy is lacking. The structural lesions discussed include arachnoid cyst, Chiari malformation Type I, cavum septum pellucidum, and the presence of ventriculoperitoneal shunts. Issues unique to this population with respect to the possibility of increased risk of head injury are addressed. The population of athletes with epilepsy and certain genetic risk factors is also discussed. Finally, the ability of athletes to participate in contact or collision sports after undergoing craniotomies for traumatic or congenital abnormalities is evaluated. Several known instances of athletes returning to contact sports following craniotomy are also reviewed.