This chapter provides information about the chemical structure of the popular thermoplastic orthodontic aligners, analyzes their mechanical properties for the as-received condition and after intraoral or artificial aging, and discusses the impact of these alterations on the efficacy of orthodontic treatment. Invisalign aligners are constructed from a thermoplastic polyurethane. Other manufacturers make greater use of polyethylene terephthalate glycol. Orthodontic forces delivered by thermoplastic appliances depend on amount of activation, material, thickness, and thermoforming process. However, in each aligner, most tooth movement occurs within the first 24 h. A strong correlation exists between mechanical properties, mainly hardness and elastic modulus, of the thermoplastic materials and force produced by the appliances. Additionally, appliances with higher hardness are expected to demonstrate better wear resistance. Aging causes a decrease of the residual stress within all materials with time and a deterioration of their clinical properties. The impact of this deterioration in tooth movement is not always clear. These materials absorb water with time and expand hygroscopically. Aligners were found not to release traceable monomers or by-products after short-term in vitro aging. Moreover, they did not seem to induce cytotoxic and estrogenic effects.