Medial tibial stress syndrome (MTSS) is one of the most common leg injuries in athletes and soldiers. The incidence of MTSS is reported as being between 4% and 35% in military personnel and athletes. The name given to this condition refers to pain on the posteromedial tibial border during exercise, with pain on palpation of the tibia over a length of at least 5 cm. Histological studies fail to provide evidence that MTSS is caused by periostitis as a result of traction. It is caused by bony resorption that outpaces bone formation of the tibial cortex. Evidence for this overloaded adaptation of the cortex is found in several studies describing MTSS findings on bone scan, magnetic resonance imaging (MRI), high-resolution computed tomography (CT) scan and dual energy x-ray absorptiometry. The diagnosis is made based on physical examination, although only one study has been conducted on this subject. Additional imaging such as bone, CT and MRI scans has been well studied but is of limited value. The prevalence of abnormal findings in asymptomatic subjects means that results should be interpreted with caution. Excessive pronation of the foot while standing and female sex were found to be intrinsic risk factors in multiple prospective studies. Other intrinsic risk factors found in single prospective studies are higher body mass index, greater internal and external ranges of hip motion, and calf girth. Previous history of MTSS was shown to be an extrinsic risk factor. The treatment of MTSS has been examined in three randomized controlled studies. In these studies rest is equal to any intervention. The use of neoprene or semi-rigid orthotics may help prevent MTSS, as evidenced by two large prospective studies.