Mastitis is one of the most common and expensive diseases in dairy cattle. The decision to treat clinical mastitis is usually made without any knowledge of the etiology, and can therefore only be evidence-based to a limited extent. Evidence-based medicine relies essentially on a combination of one's own clinical competence and scientific findings. In mastitis therapy, those insights depend mostly on pathogen-specific factors. Therefore, in evidence-based therapeutic decision making the pathogen identification should serve as a basis for the consideration of scientifically validated therapeutic concepts. The present paper considers evidence-based treatment of clinical mastitis based on a literature review. The authors conclude that an anti-inflammatory treatment using an NSAID should be conducted regardless of the pathogen. However, the choice of an antibiotic therapy depends on the mastitis causative pathogen, clinical symptoms and the animal itself. In principle, a local antibiotic treatment should be chosen for mild and moderate mastitis. It should be noted, that the benefit of an antibiotic therapy for coliform infections is questionable. With knowledge concerning the pathogen, it appears entirely reasonable to refrain from an antibiotic therapy. For severe (i.   e. feverish) mastitis, a parenteral antibiotic therapy should be selected. An extension of the antibiotic therapy beyond the manufacturer's information is only reasonable for streptococcal infections. It is important to make the decision on a prolonged antibiotic therapy only with the knowledge of the mastitis-causative pathogen. In terms of the therapy of a staphylococcus or streptococcus infection, a narrow-spectrum antibiotic from the penicillin family should be adopted when selecting the active agents.