The use of beta-lactamase inhibitors in combination with beta-lactam antibiotics is currently the most successful strategy to combat a specific resistance mechanism. Their broad spectrum of activity originates from the ability of respective inhibitors to inactivate a wide range of beta-lactamases produced by Gram-positive, Gram-negative, anaerobic and even acid-fast pathogens. Clinical experience confirms their effectiveness in the empirical treatment of respiratory, intra-abdominal, and skin and soft tissue infections. There is evidence to suggest that they are efficacious in treating patients with neutropenic fever and nosocomial infections, especially in combination with other agents. beta-Lactam/beta-lactamase inhibitor combinations are particularly useful against mixed infections. Their role in treating various multi-resistant pathogens such as Acinetobacter species and Stenotrophomonas maltophilia are gaining importance. Although, generally, they do not constitute reliable therapy against extended-spectrum beta-lactamase producers, their substitution in place of cephalosporins appears to reduce emergence of the latter pathogens. Similarly, their use may also curtail the emergence of other resistant pathogens such as Clostridium difficile and vancomycin-resistant enterococci. beta-Lactam/beta-lactamase inhibitor combinations are generally well tolerated and their oral forms provide effective outpatient therapy against many commonly encountered infections. In certain scenarios, they could even be more cost-effective than conventional combination therapies. With the accumulation of so much clinical experience, their role in the management of infections is now becoming more clearly defined.