Positional cloning of mouse deafness mutations uncovered a plethora of proteins that have important functions in the peripheral auditory system in particular in the cochlear organ of Corti and stria vascularis. Most of these mutant variants follow a monogenic form of inheritance and are rare, highly penetrant, and deleterious alleles. Inbred and heterogenous strains of mice, in contrast, present with non-syndromic hearing impairment due to the effects of multiple genes and hypomorphic and less penetrant alleles that are often transmitted in a non-Mendelian manner. Here we review hearing loss inheritance patterns as they were discovered in different strains of mice and discuss the relevance of candidate genes to late-onset progressive hearing impairment in mouse and human.