The genetic basis of thrombosis is complex, involving multiple genes and environmental factors. The field of common complex disease genetics has progressed enormously over the past 10 years with the development of powerful new molecular and analytical strategies that enable localization and identification of the causative genetic variants. During the course of these advances, a major paradigmatic change has been taking place that focuses on the genetic analysis of measurable quantitative traits that are correlated with disease risk vs. the previous emphasis on the analysis of the much less informative dichotomous disease trait. Because of their closer proximity to direct gene action, disease-related quantitative phenotypes represent our best chance to identify the underlying quantitative trait loci (QTLs) that influence disease susceptibility. This approach works best when data can be collected on extended families. Unfortunately, family-based designs are still relatively rare in thrombosis/hemostasis studies. In this review, we detail the reasons why the field would benefit from a more vigorous pursuit of modern family-based genetic studies.