The patterns of activity of masticatory and perioral muscles play an important role in craniofacial growth and development, as well as in a successful and stable outcome of orthodontic treatment. Despite this concept is commonly accepted by the whole orthodontic community, a lot of controversies still exist as to whether interventions aiming to change muscle functioning can influence the treatment outcome to a clinically relevant extent. In this lecture, the physiological aspects of orofacial muscle functioning and their relationship to craniofacial growth will be critically reviewed. Possible clinical and research implications in orthodontics will also be discussed.