Although intensive research and prevention measures have been carried out for decades to control bovine mastitis, it continues to cause the biggest economic impact to the dairy industry worldwide. Therefore, it is of great importance to investigate biomarkers that could be used for rapid detection of mastitis. The discovery of new biomarkers which allow the clinical monitoring of different diseases is nowadays encouraged in order to improve the diagnosis, evaluation, treatment and therapeutics in each phase of the disease. Therefore, the use of acute phase proteins in the diagnosis of clinical and subclinical mastitis and their application in the monitoring of treatment is considered as one of the most interesting applications of these proteins. Although a wide range of studies have been carried out to determine the role of acute phase proteins in the inflammatory diseases of the mammary gland, there is still necessity for the evaluation of their usefulness in these pathological conditions. Therefore, the acute phase response and clinical application of acute phase proteins in clinical and sub-clinical mastitis of dairy cows are discussed and evaluated in this work.