Diseases with complex inheritance are characterized by multiple genetic and environmental factors that often interact to produce clinical symptoms. In addition, etiological heterogeneity (different risk factors causing similar phenotypes) obscure the inheritance pattern among affected relatives and hamper the feasibility of gene-mapping studies. For such diseases, the careful selection of quantitative phenotypes that may represent intermediary risk factors for disease development (intermediate phenotypes) is etiologically more homogeneous than the disease per se. Over the last 15 years quantitative trait locus mapping has become a popular method for understanding the genetic basis for intermediate phenotypes. This chapter provides an introduction to classical and recent strategies for mapping quantitative trait loci in humans.