This chapter will discuss the medical, psychological, and sociocultural aspects of the autism spectrum and present the basic assumptions of psychotherapeutic work with autistic people in terms of positive and transcultural psychotherapy. Autism spectrum (AS) as a different neurodevelopmental pattern affects approximately 2% of the population. Autistic people experience different challenges in each decade of their lives. Variations in sensory-motor, emotional, communication, and cognitive functioning create challenges across intrapsychic, interpersonal, familial, and social domains. At the same time, these differences constitute the basis for developing a unique culture and solutions, often necessary for the development of societies. Knowledge, understanding, respect, awareness of the phenomenon of double empathy, and openness to neurodiversity are the basic prerequisites for Positive Psychotherapists and any professional who decides to consciously and ethically build a therapeutic relationship with an autistic person.