The prevalence of psychiatric disorders among patients with intellectual disability (ID) and low-functioning autism spectrum disorder (ASD) is higher than in the general population. The available reports on this comorbidity vary depending on the adopted methodologies, the size of the examined ID population, and the criteria used to diagnose mental disorders. Multiple factors contribute to the significantly different presentation of psychopathological symptoms and syndromes in people with ID and ASD compared to the general population, including cognitive and communicative impairments, developmental peculiarities, and neuro-autonomic vulnerability. Because they have a hard time conceptualizing and articulating their mental states, the diagnosis of their psychopathology must rely on firsthand observation of behaviors in the context of daily life as well as third-party accounts. As a result, diagnostic criteria designed for the general population are ineffective when used in these groups, so for them specific diagnostic procedures and instruments should be a significant determinant of psychiatric diagnosis validity.