The hemidesmosome (HD)-anchoring filament complex comprises a multiprotein complex that aids the attachment of epidermal keratinocytes to the underlying basal lamina and dermis. The importance of the HD and its components is highlighted by genetic defects that cause congenital blistering skin diseases that are categorised under the epidermolysis bullosa (EB) group of disorders. EB disorders can be subcategorised into three main subtypes by the level of epidermal separation – within the basal keratinocyte (EB simplex – EBS), between the keratinocyte and underlying basal lamina (junctional EB – JEB), and separation beneath the basal lamina (dystrophic EB – DEB). HD-anchoring filament-related components – including keratins 5 and 14, plectin, a6ß4 integrin, collagen XVII, laminin 332 and collagen VII – have been demonstrated to harbour defects leading to EB disease. We summarise here the current understanding of the biological function of these HD-components and their involvement in EB in light of their functions in keratinocyte adhesion and also describe putative future therapeutic avenues that hold promise to alleviate the morbidity suffered by EB patients over the coming decades.