Abstract Autism is a neurodevelopmental disorder characterized by impaired social interaction and restricted interests, compromised communication skills, and repetitive patterns of behavior. Both social and behavioral problems, which may include hyperactivity and quick frustration, may hinder the detection of other important pathologies such as orofacial pain. This is aggravated by the invasive nature of oral exploration, which may trigger violent and self-injurious responses, such as temper tantrums and/or head banging, which make the work of professionals extremely difficult during diagnoses, follow-up examinations, and dental treatments. In addition, mercury-containing amalgams used to treat dental caries (the most common form of acute orofacial pain) have been associated with higher rates of severe autism in children. The purpose of this review is to describe the current state of the art regarding the co-occurrence of orofacial pain and autism spectrum disorder, and how these conditions may interrelate clinically and neurobiologically.