Medial tibial stress syndrome (MTSS) is one of the most common lower leg injuries in athletes who run. Studies have reported MTSS to occur in 4% to 20% of this population. It can be defined as an overuse injury that creates pain over an area covering the distal to middle third of the posteriomedial tibial border, which occurs during exercise and creates cyclic loading. Differential diagnosis includes ischemic disorders and stress fractures. Although the pathology of this injury is understood, the etiology is less agreed upon. This makes it difficult for clinicians to diagnose and treat this common injury. The purpose of this article is to present health care practitioners with the most current information regarding MTSS so they can better diagnose and treat this common injury. To this end, a literature review was conducted, with the most current results presented. The areas of etiological theories, imaging techniques, and treatment options for MTSS were searched. Five of the most prevalent etiological theories are presented with supporting evidence. Of the imaging tools available to the clinician, magnetic resonance imaging (MRI) and bone scintigraphy have comparable specificity and sensitivity. Clinicians should first make the clinical diagnosis of MTSS, however, because of high percentages of positive MRI scans in asymptomatic patients. There have been few randomized controlled trials investigating treatment options for athletes with MTSS. Those that have been performed rendered no significant findings, leading researchers to conclude that rest is equal to or better than other treatment options. Given the evidence, treatment suggestions for practitioners caring for athletes with MTSS are provided.