Biofilms occur in natural aquatic ecosystems and on surfaces of biomaterials. They are generally associated with clinical infections predominantly of prosthetic hip joints, heart valves and catheters. Sessile microorganisms may be intimately associated with each other and to solid substratum through binding to and inclusion into exopolymer matrices on biofilms. The establishment of functional colonies within the exopolymeric matrices generate physico-chemical gradients within biofilms, that modify the metabolism and cell-wall properties of the microorganism. A consequence of biofilm growth is an enhanced microbial resistance to chemical antimicrobial agents and antibiotics. Investigations on the antimicrobial efficacy of antibiotics, antiseptics and antimicrobial heavy ions, however, gave controversial results. No single antimicrobial substance has been developed for the efficient eradication of adherent bacteria. This review elucidates the mechanisms of microbial resistance in biofilms and strategies for the prevention of biofilm development. Pharmacokinetical and pharmacodynamical issues for the screening of biofilm-active drugs are presented. Combinations of antistaphylococcal antibiotics with rifampin may be advantageous for preventing and curing biomaterial infections.