For many years, the mainstay of pediatric genetic testing was chromosomal analysis. Based on a technology developed in the 1950s and refined in the 1960s, this approach permitted the detection of abnormalities of chromosome number and some structural rearrangements. The past decade has seen an explosion in knowledge about the genetic basis of disease, and accompanying this, the development of new types of diagnostic tests. This article reviews some of these new approaches, and provides a practical guide for the pediatrician who is increasingly called upon to arrange for such testing and to interpret the results.