From studies with peas over 150 years ago, Gregor Mendel deduced the laws that govern the inheritance of traits in most organisms. The brilliance, but also the limitation, of Mendel's work was its focus on single-gene traits, such as flower color and plant height. However, phenotypic variation, including that which underlies health and disease in humans, often results from multiple interactions among numerous genetic and environmental factors. Systems genetics seeks to understand this complexity by integrating the questions and methods of systems biology with those of genetics to solve the fundamental problem of interrelating genotype and phenotype in complex traits and disease.