Introduction: Recently, several reviews have been published on the effects of medications on bone physiology and the clinical side effects in orthodontics. However, the effects of medications on the rate of orthodontic tooth movement have not been evaluated. Methods: A systematic literature review on the effects of medications and dietary supplements on the rate of experimental tooth movement was performed by using PubMed (1953-Oct 2007), Web of Science, and Biosis, complemented by a hand search. Results: Forty-nine articles were included in the review, but their interpretation was hindered by the variability in experimental design, magnitude of force applied during tooth movement, and medication regimens. Therapeutic administration of eicosanoids resulted in increased tooth movement, whereas their blocking led to a decrease. Nonsteroidal anti-inflammatory drugs (NSAIDs) decreased tooth movement, but non-NSAID analgesics, such as paracetamol (acetaminophen), had no effect. Corticosteroid hormones, parathyroid hormone, and thyroxin have all been shown to increase tooth movement. Estrogens probably reduce tooth movement, although no direct evidence is available. Vitamin D3 stimulates tooth movement, and dietary calcium seemed to reduce it. Bisphosphonates had a strong inhibitory effect. Conclusions: Medications might have an important influence on the rate of tooth movement, and information on their consumption is essential to adequately discuss treatment planning with patients. (Am J Orthod Dentofacial Orthop 2009;135: 16-26) R ecently, several reviews have been published about the biologic processes related to orth-odontic tooth movement (OTM). 1-4 These re-views describe similar reactions of periodontal cells and extracellular matrices to orthodontic force applica-tion. Briefly, the principal trigger for OTM is probably strain of the periodontal ligament cells, bone-related cells, and the extracellular matrix. 3 This strain leads to changes in gene expression in the cells by interactions between the cells and the extracellular matrix, whereby integrins play an important role. 2 Various cell-signaling pathways are activated, which ultimately lead to stim-ulation of periodontal ligament turnover, and localized bone resorption and bone deposition. 2-4 In addition, recent reviews by several authors have been published on the effects of systemic or local application of medications and the intake of dietary supplements, such as vitamins and minerals, during OTM. 5-7 In most cases, these reviews distinguish 2 categories of effects: those related to general bone physiology in terms of bone density, bone mineraliza-tion, bone turnover rate, and osteoclast differentiation; and clinical side effects induced by medications, such as gingival hyperplasia, xerostomia, and external root resorption. 5-7 Most reviews, however, did not report experimental data on the effects of medications or dietary supplements on the rate of OTM. 7-10 Nonetheless, such information is important for clinicians in communications with patients, because many patients use prescription and over-the-counter medications, as well as dietary supplements daily. Consequently, these substances can affect both the rate of OTM and the expected duration of treatment. 6,7,11 Therefore, we performed a systematic literature review based on experimental data on the sequelae of pharmaceutical interventions and the use of dietary supplements on the rate of OTM. Unfortunately, only a few human clinical trials have been published. 12-14 As a result, this review focuses mainly on well-controlled animal studies. Our review is organized around several regulatory systems of which disturbances might lead to pathologic