A full working knowledge of disease, genetic mechanisms, epidemiology, genotyping, and statistical analysis is essential for successful study of complex disease. There have been major advances in the understanding of genetic mechanisms of disease and translation of this understanding to clinical practice. This chapter discusses genetic models and describes the basic methods currently used to conduct complex trait inheritance research. The future discoveries will be made by teams of researchers cooperating to integrate all parts, including clinicians, laboratory scientists, biostatisticians, bioinformaticians, and pharmaceutical designers. The thoughtful application of discoveries to cure or ameliorate diseases will be a great challenge to clinicians as we enter a new age of genomic medicine. It will lead to new insights into pathophysiology and to the development of new approaches to diagnosis, prevention, and treatment. © 2007 Elsevier Inc. All rights reserved.