Genetic mapping by linkage analysis has been an invaluable tool in the positional strategy to identify the molecular basis of many rare Mendelian disorders. With the attention of the scientific and medical community shifting towards the analysis of more common, complex traits, it has become necessary to develop new approaches that take into account the complexity of the genetic basis of these disorders and their possible interaction with other, nongenetic factors. Linkage disequilibrium studies are now becoming increasingly popular thanks to the advent of genotyping platforms that allow genome-wide searching for association between hundreds of thousands of random polymorphisms and disease phenotypes in large samples of unrelated individuals. Moreover, the definition of the disease phenotype itself is being reconsidered to include quantitative traits that may better define the underlying biologic mechanisms for many pathologic conditions. This article will review classic and new approaches to genetic mapping by linkage and association analysis and discuss the directions this field is likely to take in the near future.