Recombinant DNA technology has made possible the localization and isolation of disease-related genes, the tracking of disease-related alleles through family pedigrees, the direct detection of the pathological lesion itself and the in vitro expression of both normal and mutant genetic information at the mRNA and protein levels. Undoubtedly the most immediate practical spin-off from recombinant DNA technology in medical genetics has been in the sphere of improved disease diagnosis and prediction, where advances have been dramatic. We review the nature of inherited disease, current approaches to its analysis, diagnosis and prediction, mechanisms of gene mutation and the available techniques for mutation detection. Also examined are the various genetic factors that can alter the relationship between genotype and clinical phenotype. Finally, the genetics of selected adult-onset disorders are explored in the context of considering the accuracy and reliability of disease prediction.