Autism spectrum disorder (ASD) is a neurodevelopmental disorder characterized by deficits in social communication and social interaction and restricted, repetitive patterns of behavior, interests, or activities. The etiology of the disorder is still not entirely known, and there are efforts to explain its roots in genetic and environmental factors. About 20 % of children with this disorder are experiencing difficulties because of irritability which is being recognized as an additional symptom of the disorder and is burdensome for the child's development and progress in the field of social interactions, as well as for their families and caregivers. Literature offers several definitions of irritability, but according to neuroscientific research, it would be best to define it as aberrant responses to frustration (i.e., blocked goal attainment) or aberrant approach responses to threat. When methods targeting core symptoms of ASD fail to improve severe symptoms of irritability, clinicians are trying to introduce new methods to yield improvements. Risperidone and aripiprazole are currently the only two medications approved for this indication in the USA, but they are sometimes also prescribed in European countries, although off label. Except for risperidone and aripiprazole, which are antipsychotics, there are research studies and reports on usage of some other psychoactive medications. When treating children, it is preferred to begin the attempt to reduce symptoms of irritability with nonpharmacological treatments to avoid side effects of medications. To this end, efforts are being made in implementation of parent training, therapeutic horse riding and new technologies in the treatment program. These methods could be particularly useful in preventing exacerbation of symptoms of irritability when they are still mild.