This review aimed to evaluate studies on cytokines in the gingival crevicular fluid (GCF) during orthodontic treatment, summarizing the regulation patterns of the most commonly studied cytokines and exploring their clinical implications. To achieve this, a number of key databases were searched using MESH terms and free text terms. An additional search was made by reference tracking. The procedures suggested by the QUOROM statement were followed. Data from the included studies were extracted into orthodontic mechanics, GCF sampling/handling methods, and cytokine measurements. From the 85 relevant studies identified, 23 studies could be included. Common drawbacks consisted mainly of inadequacies in the study design (e.g. short duration and small number of study subjects). The most consistent result was a peak of cytokine levels at 24 h. Associations existed between prostaglandin E(2) (PGE(2)) and interleukin-1beta (IL-1beta) and pain, velocity of tooth movement, and treatment mechanics. Interleukin-1beta and PGE(2) showed different patterns of up-regulation, with IL-1beta being more responsive to mechanical stress and PGE(2) more responsive to synergistic regulation of IL-1beta and mechanical force. The results might be taken to support, at the cellular level, the use of light continuous forces for orthodontic treatment.