Many people are exposed to environmental risk factors for fibrosis, yet only a subset go on to develop disease. It is likely that a number of tissue-specific disease genes determine the path an individual will follow upon exposure to an environmental agent, and that individuals who carry certain combinations of these genes are most susceptible. Diseases which have multiple genetic and environmental determinants, known as "complex traits," present a formidable challenge for gene discovery as the combined influence of more than one gene and one or more environmental factors decrease power to isolate the effect of any single gene. Nevertheless, the identification of the genetic differences that underlie susceptibility to fibrotic disease is crucial to understanding the disease process and to the development of effective screening tests and treatments. No single strategy or method will likely be sufficient to link a candidate disease gene to a fibrosis phenotype. Therefore, we present techniques and resources that can be used in combination to dissect the genetics of complex traits and yield viable candidate genes. Testing of candidate genes and standards for formal proof of gene discovery are discussed.