Chronic exertional compartment syndrome (CECS) of the lower limb is part of a group of overuse lower limb injuries with common presenting features. It is commonly diagnosed by the measurement of raised intramuscular pressures in the lower limb. The pathophysiology of the condition is poorly understood, and the criteria used to make the diagnosis are based on small sample sizes of symptomatic patients. We carried out a systematic review to compare intramuscular pressures in the anterior compartment of healthy subjects with commonly used criteria for CECS. Thirty-eight studies were included. With the exception of relaxation pressure, the current criteria for diagnosing CECS, considered to be the gold standard, overlap the range found in normal healthy subjects. Several studies reported mean pressures that would prompt a positive diagnosis for CECS, despite none of the subjects reporting any symptoms. The intramuscular pressure at all time points has also shown to vary in relation to a number of other factors other than the presence of CECS. Taken together, these data have major implications on the ability to use these published criteria for diagnosis and question the underlying pathophysiology. Clinicians are recommended to use protocol-specific upper confidence limits to guide the diagnosis following a failed conservative management.