This article briefly describes the mechanisms of cranio-facial growth and the role of the forming functions (namely mastication, breathing, swallowing and speech) in achieving a harmonious development. Facial sutures are joints and important sites of bone growth with visco-elastic characteristics that distribute forces to the whole cranial structure that remain well into adulthood. An equally important role is played by the temporomandibular joint, which undergoes a major change in morphology during growth, constantly accompanying the changing oral functions (from suction to mastication and speech); the mandibular condyle is an important site of bone growth, with a large capacity to adapt or to compensate. The ability of this joint to compensate is a lifelong adaptive process that takes place in interplay with everchanging occlusal conditions. The temporomandibular joint’s dramatic involvement in children affected by juvenile idiopathic arthritis is quite obvious, with or without signs or symptoms. Some malocclusions, and the cross-bites in particular, alter both the occlusion and the masticatory function, leading to an altered cranial development that is irreversible at the end of growth. Recently, laboratory and clinical research have highlighted, in animal models of reduced mastication, an association between the experimental reduction of the masticatory function and a significantly reduced number of hippocampal neurons, neurogenesis in the dentate gyrus, synaptic density, and increased glial activity, as well as reduced memory and spatial orientation. Mastication is, therefore, central to the craniofacial development of the child and the development of cognitive functions. Therefore, the treatment of malocclusions must be respectful of physiology and biology to re-establish all the functions of the growing stomatognathic apparatus and avoid traumatic treatments whose effects are impossible to anticipate and prevent, given the developing system’s complexity and its importance for future functional and cognitive balance.