Twin studies have had a key role in the evaluation of heritability, a population-based estimate of the genetic contribution to phenotypic variation. These studies have led to the revelation that most normal and disease phenotypes are to some extent heritable. Recently, interest has shifted from phenomenological heritability to the identification of trait-specific genes. The era of twin studies, however, is not over: recent epigenetic and global gene expression studies suggest that the most interesting findings in twin-based research are still to come. The increasing realization of the influence of epigenetics in phenotypic outcomes means that the molecular mechanisms behind phenotypic differences in genetically identical organisms can be explored. Analyses of epigenetic twin differences and similarities might yet challenge the fundamental principles of complex biology, primarily the dogma that complex phenotypes result from DNA sequence variants interacting with the environment.