The etiology of chronic rhinosinusitis (CRS) remains unclear. Study of the genetic susceptibility to CRS may be a valuable strategy to understand the pathogenesis of this burdensome disorder. The purpose of this review is to critically evaluate the current literature regarding the genetics of CRS in a comprehensive fashion. The most promising findings from candidate gene studies include the Cystic Fibrosis Transmembrane Conductance Regulator gene (CFTR), as well as genes involved in antigen presentation, innate and adaptive immune responses, tissue remodeling, and arachidonic acid metabolism. We also review the few hypothesis-independent genetic studies of CRS (i.e., linkage analysis and pooling-based genome-wide association studies). Interpretation of the current literature is limited by challenges with study design, sparse replication, few functional correlates of associated polymorphisms, and inadequate examination of linkage disequilibrium or expression quantitative trait loci for reported associations. Given the relationship of CRS to other airway disorders with well-characterized genetic components (e.g., asthma), study of the genetics of CRS deserves increased attention and investment, including the organization of large, detailed, and collaborative studies to advance knowledge of the mechanisms that underlie this disorder.