SYNOPSIS: Bone stress injury (BSI) represents the inability of bone to withstand repetitive loading, which results in structural fatigue and localized bone pain and tenderness. A BSI occurs along a pathology continuum that begins with a stress reaction, which can progress to a stress fracture and, ultimately, a complete bone fracture. Bone stress injuries are a source of concern in long-distance runners, not only because of their frequency and the morbidity they cause but also because of their tendency to recur. While most BSIs readily heal following a period of modified loading and a progressive return to running activities, the high recurrence rate of BSIs signals a need to address their underlying causative factors. A BSI results from disruption of the homeostasis between microdamage formation and its removal. Microdamage accumulation and subsequent risk for development of a BSI are related both to the load applied to a bone and to the ability of the bone to resist load. The former is more amenable to intervention and may be modified by interventions aimed at training-program design, reducing impact-related forces (eg, instructing an athlete to run "softer" or with a higher stride rate), and increasing the strength and/or endurance of local musculature (eg, strengthening the calf for tibial BSIs and the foot intrinsics for BSIs of the metatarsals). Similarly, malalignments and abnormal movement patterns should be explored and addressed. The current commentary discusses management and prevention of BSIs in runners. In doing so, information is provided on the pathophysiology, epidemiology, risk factors, clinical diagnosis, and classification of BSIs. LEVEL OF EVIDENCE: Therapy, level 5.