Personality disorders (PD) might be considered as extremes of personality dimensions varying in the general population or as attenuated variants of major psychiatric disorders. Both personality variation and major psychiatric disorders have been shown in twin and adoption studies, to be influenced by genes. Hence, it is likely that personality disorders are also under genetic control. However, direct evidence for influential familial and genetic factors is scarce. Various research strategies in this area are described and current evidence is reported. Gene-oriented approaches seem to be particularly promising. This strategy is illustrated for personality disorders in obligate carriers of mutations in the fragile-X gene.