The principal distinction between “simple” monogenic diseases and “complex” diseases is that the latter do not exhibit classic patterns of Mendelian inheritance. Complex diseases tend to involve greater difficulties in phenotype definition and present challenges for genetic epidemiology. There is, typically, incomplete penetrance and genetic heterogeneity and they are often closely associated with “intermediate” phenotypes that are themselves highly heritable. The use of isolated populations, inbred animal models, and linkage and association analysis with haplotypes are often used in the study of complex diseases.