Prostate cancer (PC) is a pervasive disease both in terms of incidence and mortality, yet little is known about its etiologic factors. Twin and segregation studies provide evidence for an inherited genetic component to the etiology of PC, yet over a dozen family-based genetic linkage analyses have not been able to consistently identify susceptibility loci. This chapter will review these studies, describe the challenges of this endeavor, and describe efforts to confront these challenges, such as using larger sets of families and more homogeneous subgroups.