Family-based designs are commonly used in genetic association studies to identify and to locate genes that underlie complex diseases. In this paper, we review two examples of genome-wide association studies using family-based cohort studies, including the Framingham Heart Study and International Multi-Center ADHD Genetics Project. We also review statistical methods of family-based designs, including the transmission disequilibrium test (TDT), linkage analysis, and imprinting effect analysis. In addition, we evaluate the strengths and limitations of the family-based cohort design. Despite the costs and difficulties in carrying out this type of study, a family-based cohort study can play avery important role in genome wide studies. First, the design will be free from biases due to population heterogeneity or stratification. Moreover, family-based designs provide the opportunity to conduct joint tests of linkage and association. Finally, family-based designs also allow access to epigenetic phenomena like imprinting. The family-based cohort design should be given careful consideration in planning new studies for genome-wide strategies.