<b><i>Background:</i></b> Low-frequency non-syndromic hearing loss (LFNSHL) is a rare form of hearing loss (HL). It is defined as HL at low frequencies (≤2,000 Hz) resulting in a characteristic ascending audiogram. LFNSHL is usually diagnosed postlingually and is progressive, leading to HL affecting other frequencies as well. Sometimes it occurs with tinnitus. Around half of the diagnosed prelingual HL cases have a genetic cause and it is usually inherited in an autosomal recessive mode. Postlingual HL caused by genetic changes generally has an autosomal dominant pattern of inheritance and its incidence remains unknown. <b><i>Summary:</i></b> To date, only a handful of genes have been found as causing LFNSHL: well-established <i>WFS1</i> and, reported in some cases, <i>DIAPH1</i>, <i>MYO7A</i>, <i>TNC</i>, and <i>CCDC50</i> (respectively, responsible for DFNA6/14/38, DFNA1, DFNA11, DFNA56, and DFNA44). In this review, we set out audiological phenotypes, causative genetic changes, and molecular mechanisms leading to the development of LFNSHL. <b><i>Key Messages:</i></b> LFNSHL is most commonly caused by pathogenic variants in the <i>WFS1</i> gene, but it is also important to consider changes in other HL genes, which may result in similar audiological phenotype.