The great successes in the treatment of childhood cancers have been followed in recent years with a new understanding of the molecular genetic abnormalities that underlie their origin. For some cancers these genetic changes are in oncogenes; in others, they are in antioncogenes, or tumor suppressor genes. Initiating aberrations in the former are associated characteristically with chromosomal translocations, the analysis of which should soon lead to the identification of oncogenes other than those in the myc family. Several tumor suppressor genes of importance in the childhood cancers have been cloned and others should soon follow. It is reasonable to expect that during the current decade molecular understanding of the genetic defects in the major pediatric cancers will be achieved. The knowledge gained through these studies, past and future, may provide new approaches to prevention and treatment and lead to additional progress.