Despite the enormous heterogeneity of genetic hearing loss, variants in one locus, Gap Junction Beta 2 or GJB2 (connexin 26), account for up to 50% of cases of nonsyndromic sensorineural hearing loss in some populations. This article reviews genetic epidemiology studies of the alleles of GJB2, prevalence rates, genotype-phenotype relations, contribution to the incidence of hearing loss, and other issues related to the clinical validity of genetic testing for GJB2. This review focuses primarily on three alleles: 167 Delta T, 35 Delta G, and 235 Delta C. These alleles are recessive for nonsyndromic prelingual sensorineural hearing loss, and the evidence suggests complete penetrance but variable expressivity.