Recent advances in molecular biology make genetic linkage analysis an increasingly attractive tool for the identification and characterization of genes involved in the etiology of psychiatric illnesses. However, the complex nature of psychiatric illnesses engenders a host of methodological difficulties not encountered in linkage analyses of simple, Mendelian genetic traits. A previous paper reviewed the basic concepts of genetic linkage analysis. This paper focuses on the methodological difficulties associated with the application of genetic linkage methods to psychiatric illnesses.