Significant advances in linkage studies have occurred the past decade based on the use of polymorphic DNA markers known as restriction fragment length polymorphisms (RFLPs). This approach has led to the chromosomal localization of a number of important genetic diseases, and is being increasingly applied to schizophrenia. We discuss two strategies for performing linkage studies in schizophrenia, one based on methodical testing of the human genome, and the other based on selective use of markers. The selective approach uses data from the mode of transmission, previous linkage studies, cytogenetic studies, association studies, case reports, and candidate genes to identify markers that may have an increased likelihood for linkage.