With ongoing efforts to make wool more competitive alongside other fibres, notably synthetics, there is a need to obtain a better understanding of the relationship between protein composition and characteristic wool properties to assist sheep breeding programmes. Before this can be achieved, the wool proteome needs to be mapped, by gel and non-gel techniques, and methods developed to reliably quantitate protein expression. Nevertheless, in setting out to achieve this, there are numerous challenges to be faced in the application of proteomics to wool, including the relative lack of wool protein sequence information in the publically accessible databases, the wide variety of proteins in the wool fibre, the high homology within the Type I and Type II keratins, the high degree of homology and polymorphism within individual keratin associated protein families, the dominance of the keratin proteins over others in wool and the peculiar chemistries found in keratins and their associated proteins. This review will discuss the various strategies that have been developed to both identify these proteins in the wool protein map and quantify them with the view to their application to the identification of markers for wool quality traits.