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Professional football is one of the most popular sports in the United States. There is a common constellation of injuries that are seen frequently. Much attention has been focused on concussions and their long-term outcomes in this population. Other common causes of morbidity include cervical spine injuries, knee injuries including anterior cruciate ligament and other ligamentous injuries, ankle sprains, and medical issues including cardiac and sickle trait. Several recent studies have focused on hip impingement and hamstring injuries, among others, as sources of missed playing time as well. This review describes some of the frequently seen injuries and medical issues in professional football players. Proper management of both medical disease and on-field injuries can reduce morbidity and may lead to faster return to play and reduced risk of future injury.