Many investigators are turning their efforts to dissecting the etiology of complex traits. The primary tools for gene discovery, localization, and functional analysis are linkage and association studies. While the conceptual underpinnings of these approaches have long been known, advances in recent decades in molecular genetics, in the development of efficient computational algorithms, and in computing power have enabled the large-scale application of these methods. Here, we review the biological basis of linkage and association among loci and the common methods used to assess these relationships with respect to observed phenotypes. We further consider the two most common approaches--genome scans and candidate gene studies--especially their respective strengths, weaknesses, and resource requirements. Finally, we highlight some of the major challenges that arise from these investigative approaches and those that are inherent in the nature of complex traits. The chapters that follow elaborate on many of these topics.