Meniere disease (MD) represents a heterogeneous group of relatively rare disorders of the inner ear that causes vertigo attacks, fluctuating sensorineural hearing loss (SNHL) involving low and medium frequencies, tinnitus, and aural fullness. MD has been attributed to an accumulation of endolymph in the cochlear duct. The diagnosis of MD is based on the phenomenological association of clinical symptoms including SNHL during the vertigo attacks. At least two mechanisms are involved in MD: (a) a pro-inflammatory immune response mediated by interleukin-1 beta (IL-1β), tumor necrosis factor alpha (TNFα), and IL-6, and (b) nuclear factor-kappa B (NF-κB)-mediated inflammation in the carriers of the single nucleotide variant rs4947296. The majority of MD cases are considered sporadic, although familial aggregation has been recognized in European and East Asian populations in multiplex families, supporting a genetic contribution to the disease. In sporadic MD cases, the main genetic findings involve multiplex rare variants in several SNHL genes, such as GJB2, USH1G, SLC26A4, ESRRB , and CLDN14 , and axonal guidance signaling genes, such as NTN4 and NOX3 . Familial aggregation has been reported in 6–8 % of MD cases, and most families show an autosomal dominant inheritance. Few rare missense heterozygous variants have been described in simplex families in six genes ( COCH , FAM136A , DTNA , PRKCB , SEMA3D , and DPT ). Of note, 33 % of familial MD individuals show singleton and multiplex rare missense variants in the OTOG gene, suggesting a multiallelic inheritance. Moreover, potentially pathogenic rare variants in the familial genes FAM136A , DTNA , and DPT have been reported in Korean singletons with sporadic MD. Rare variants may have a significant contribution to sporadic and familial MD. The interaction of common cis-regulatory variants located in non-coding regions and rare variants in coding regions in one or more genes will determine the variation on the phenotype in MD. Further studies on genotype–phenotype correlations are required to improve the yield of genetic diagnosis, and different types of variants seem to contribute to the genetic structure of MD.