Until recently, the cause of intellectual disability remained unknown in at least 50% of affected people. The various causes require diverse healthcare needs. Knowing the cause enables specific anticipation on these. Severe intellectual disability (IQ < 50) usually has a genetic cause. The majority can be explained by de novo gene mutations and chromosomal aberrations. In recent years, rapid advances in genetic diagnostics have provided great new opportunities. The introduction of array analysis has allowed the genome-wide detection of chromosomal aberrations. Until recently, the detection of monogenic causes of intellectual disability was highly dependent on the recognisability of the phenotype and specific DNA diagnostic testing of single genes. The introduction of exome sequencing enables testing of all genes simultaneously in a single test. It is expected that exome sequencing will be followed up by genome sequencing in the near future, and this will become the first tier diagnostic test. Detection of chromosomal aberrations is also possible with this technique. These developments may lead to a significant increase in the percentage of explained intellectual disability, from 50% in the past to 80%.