He is famous for his research on neurodevelopmental disorders, particularly for his description of Rett syndrome, which was named after him, and for pioneering treatment based on the belief that disabled children also have a right to fulfillment of their physical, emotional, and psychological needs.

He then trained in paediatrics, and in 1955 he was appointed head of the facility for children with Down Syndrome at a home for the aged in Lainz, Vienna.

Rett's academic career began in 1967, when he was appointed as lecturer in neurology and pediatrics at the University of Vienna, in 1973 being promoted to the rank of associate professor.

After Rett's death, he received criticism for having been listed as a member of the Hitler Jugend and the Nazi Party as a child and young adult.

In recent years he has also been criticized for using research data derived from the Nazi program of Action T4, which was the name given to the mass murder of hundreds of thousands of people, including of children, under the guise of medical euthanasia.