Keratins are important structural proteins produced by mammals, birds and reptiles. Keratins usually act as a protective barrier or a mechanical support. Millions of tonnes of keratin wastes and low value co-products are generated every year in the poultry, meat processing, leather and wool industries. Keratinases are proteases able to breakdown keratin providing a unique opportunity of hydrolysing keratin materials like mammalian hair, wool and feathers under mild conditions. These mild conditions ameliorate the problem of unwanted amino acid modification that usually occurs with thermochemical alternatives. Keratinase hydrolysis addresses the waste problem by producing valuable peptide mixes. Identifying keratinases is an inherent problem associated with the search for new enzymes due to the challenge of predicting protease substrate specificity. Here, we present a comprehensive review of twenty sequenced peptidases with keratinolytic activity from the serine protease and metalloprotease families. The review compares their biochemical activities and highlights the difficulties associated with the interpretation of these data. Potential applications of keratinases and keratin hydrolysates generated with these enzymes are also discussed. The review concludes with a critical discussion of the need for standardized assays and increased number of sequenced keratinases, which would allow a meaningful comparison of the biochemical traits, phylogeny and keratinase sequences. This deeper understanding would facilitate the search of the vast peptidase family sequence space for novel keratinases with industrial potential.