A diagnosis of autistic spectrum disorder (ASD), now estimated to affect one in 88 children, requires deficits in social communication and interactions, and restricted interests and/or repetitive behaviors. Almost all children with ASD have deficits in adaptive skills, many have intellectual disability, and others have co-occurring psychiatric disorders or symptoms. Thus, this complex disorder has shown to have a substantial impact on patients' quality of life (QoL) and that of their families. Medication treatment is considered by clinicians and families to address problems with functioning due to psychiatric problems, and, as such, one-third of children and adolescents with ASD take at least one psychotropic medication and many use complementary and alternative medicine. This paper reviews what is known about the benefits and risks of psychotropic medications on the QoL of children with ASD. Although scarce, there are studies of psychiatric medications in autistic patients that include QoL measures, such as the pediatric studies of aripiprazole for irritability and one adult study of oxytocin. The aripiprazole study showed a positive effect on QoL in treated patients, as did the oxytocin study. Several other psychotropic medications are used in the treatment of children with ASD, and although information is available on the risks and benefits of each, we do not have specific data on the QoL impact of these medications. The aripiprazole and oxytocin studies exemplify how researchers can include QoL measures and use this information to guide clinicians. Additionally, we will recommend areas of further study in pharmacotherapy and QoL research in the context of treating children with ASD.