Structured Abstract Authors – Krishnan V, Davidovitch Z Objective – Molecules produced in various diseased tissues, or drugs and nutrients consumed regularly by patients, can reach the mechanically stressed paradental tissues through the circulation, and interact with local target cells. The combined effect of mechanical forces and one or more of these agents may be inhibitory, additive or synergistic. The objective of this review is to outline the mechanisms of action and effects of some commonly used drugs on tissue remodeling and orthodontic tooth movement. Design – All the existing published literature on the effects of various drugs that are prescribed by orthodontists, which are consumed by patients for systemic diseases and those that are known to promote and retard the tooth movement process was obtained and subjected to thorough review process. Results – All the drugs reviewed have therapeutic effects, as well as side effects, that may influence the cells targeted by orthodontic forces. Therefore, it is imperative that the orthodontist pays close attention to the drug consumption history of each and every patient, before and during the course of orthodontic treatment. When the use of drugs is revealed, their effects and side effects on tissue systems should be explored, to determine their potential influence on the outcome of mechanotherapy. Conclusion – Drug‐consumption history must be an integral part of every orthodontic diagnosis and treatment plan.