The virulence of Staphylococcus epidermidis is related to its capacity to form biofilms. Such biofilm-related infections are extremely difficult to treat and to detect in early stages by the traditional microbiological analyses. The determination of the chemical composition of the extracellular polymeric substances (EPS) of the biofilm matrix, as well as the elucidation of the sensitivity of biofilms to enzymatic degradation should facilitate the development of new therapies against biofilm-related infections. The chemical analyses of EPS had shown qualitative and quantitative variations of their nature, depending on the strains and culture conditions. The poly-N-acetylglucosamine (PNAG) is considered the main component of staphylococcal biofilms. However, certain strains form biofilms without PNAG. In addition to PNAG and proteins, extracellular teichoic acid was identified as a new component of the staphylococcal biofilms. The sensitivity of staphylococcal biofilms to enzymatic treatments depended on their relative chemical composition, and a PNAG-degrading enzyme, in conjunction with proteases, could be an efficient solution to eliminate the staphylococcal biofilms. A detection of specific ‘antibiofilm’ antibodies in the blood serum of patients could serve as a convenient noninvasive and inexpensive diagnostic tool for the detection of foreign body-associated staphylococcal infections. Used as a coating antigen in the enzyme-linked immunosorbent assay test, PNAG did not sufficiently discriminate healthy individuals from the infected patients.