Some of the important contributions of Mendel, Fisher and others during the 20th century in the development of population genetic models are reviewed, followed by a review of the four major areas of genetic epidemiology used for gene discovery: familial aggregation, segregation, co-segregation and association. It is shown how the latest methods currently being used have their theoretical basis in developments made in the early part of the century. Finally, there is speculation about what will be the main areas in biometrical genetics developed in the 21st century.