Degenerative skeletal disorders are common and serious problems worldwide, especially in aging populations. They are polygenic diseases influenced by both genetic and environmental factors, and hence the identification of susceptibility genes may provide clues to their etiology and pathogenesis, although this is still in its early stages. This review focuses on genetic studies of two representative degenerative skeletal disorders: osteoarthritis and degenerative disc disease. Genetic studies of these two diseases share common features and face similar problems, although their current statuses are very different. The two diseases have common susceptibility alleles--namely, the GDF5 rs143383 single-nucleotide polymorphism and the asporin D14 triplet repeat--which provides hints on how to investigate their genetic factors. The future success of genetic studies of these diseases will depend on accurate and reliable diagnostics, large-scale interpopulation association studies and replications, and consideration of environmental effects and related diseases with similar phenotypes.