The gingival crevicular fluid (GCF) flow rate and composition vary according to the condition of the periodontal tissues. The levels of some of its constituents have been shown to correlate with the actual clinical measurements of periodontal disease progression and reflect changes occurring deep in the periodontium. During the course of orthodontic treatment, the forces exerted produce a distortion of the periodontal ligament extracellular matrix, resulting in alterations in cellular shape and cytoskeletal configuration. Such events lead to the synthesis and presence in the deeper periodontal tissues of extracellular matrix components, tissue-degrading enzymes, acids, and inflammatory mediators; induce cellular proliferation and differentiation; and promote wound healing and tissue remodeling. These changes may modify both the GCF flow rate and its components. Consequently, analysis of GCF samples may provide a better understanding of the biochemical processes associated with tooth movement and may help the clinician make therapeutic choices based on qualitative and quantitative information.