The perioperative management of pediatric patients with psycho-physical disorders with related relational and cognitive problems must be carefully planned, in order to make the entire hospitalization process as comfortable and as less traumatic as possible. This article reports an overview of the anesthetic management of non-cooperative patients between 6 and 14 years old. The pathologies most frequently responsible for psycho-physical disorders can be summarized into three groups: (1) collaboration difficulties (autism spectrum disorders, intellectual impairment, phobia); (2) motor dysfunction (cerebral palsy, epilepsy, other brain pathologies, neuromuscular disorders), and (3) craniofacial anomalies (Down syndrome, other genetic syndromes). Anesthesia can be performed safely and successfully due to careful management of all specific problems of these patients, such as a difficult preoperative evaluation (medical history, physical examination, blood sampling, evaluation of vital parameters and predictive indices of difficult airway) and the inapplicability of a "standard" perioperative path (timing and length of the hospitalization, anesthetic premedication, postoperative management). It is necessary to ensure a dedicated perioperative process that is safe, comfortable, tailored to specific needs, and as less traumatic as possible. At the same time, all necessary precautions must be taken to minimize possible complications.