Foot orthoses have long been prescribed by health care professionals for the prevention and treatment of lower limb musculoskeletal overuse conditions. A systematic review of the literature and meta-analysis of pooled data, where appropriate, was conducted to establish the clinical efficacy and cost effectiveness of foot orthoses in the management of overuse conditions. A highly sensitive search strategy identified 23 studies (from 22 publications) that met the criteria for inclusion. Ratings of methodological quality on a Modified PEDro Scale ranged from two to 11 out of 14 (mean = 5.8), which were not significantly correlated with effect size. Evidence from the meta-analysis supports the use of foot orthoses in asymptomatic individuals to prevent lower limb overuse conditions. There is insufficient evidence to support or refute the use of foot orthoses in the treatment of patients with symptoms. Pooled evidence shows that there is no difference in outcome between custom- or pre-fabricated foot orthoses. The pooled evidence paralleled data from individual studies for which data pooling was not possible. In order to progress the evidence base for foot orthoses, future research should focus on issues such as consistent use of outcome measures across studies, longer time frame of the trials, specific definitions of the orthoses and the use of adequate control comparators.