The objective of this review is to describe the usage and applicability of proteomics technologies in the study of mastitis in ewes. In ewes, proteomics technologies have been employed for furthering knowledge in mastitis caused by various agents (Staphylococcus aureus, Staphylococcus chromogenes, Mannheimia haemolytica, Streptococcus uberis, Mycoplasma agalactiae). Studies have focused on improving knowledge regarding pathogenesis of the infections and identifying biomarkers for its diagnosis. Findings have revealed that ewes with mastitis mount a defence response, controlled by many proteins and over various mechanisms and pathways, which are interdependent at various points. Many proteins can participate in this process. Moreover, as the result of proteomics studies, cathelicidins and serum amyloid A have been identified as proteins that can be used as biomarkers for improved diagnosis of the disease. In the long term, proteomics will contribute to improvements in the elucidation of the pathogenesis of mastitis. Further in-depth investigations into the various proteomes and application of new methodological strategies in experimental and clinical studies will provide information about mastitis processes, which will be of benefit in controlling the disease. Improvement of diagnostic techniques, establishment of prognostic tools and development of vaccines are key areas for targeted research.