We review the advances that have been achieved using molecular genetic techniques to characterise the genetic basis of mental retardation in recognised syndromes and in discovering new genetic conditions that give rise to mental retardation. However, even with the cloning of a number of mutant genes, the pathogenesis of the condition is not understood. The genetics of mental retardation are turning out to be remarkably complex and are likely to remain a challenge for clinicians and scientists for years to come.