Bacterial resistance to antibiotic is the inevitable consequence of the utilization of antimicrobial agents all over the world, particularly in developed countries. It is particularly evident with beta-lactam agents because they are among most frequently prescribed drugs. The resistance is mainly attributable to production of various types of beta-lactamases but other mechanisms like alterations in PBP molecules or in outer membrane proteins can play a significant role. Increased resistance can be seen among fastidious gram-negative bacteria like Haemophilus influenzae or Moraxella catarrhalis. The percentage of M. catarrhalis isolates producing beta-lactamases has increased to over 90%. Among Enterobacteriaceae E. coli and Klebsiella pneumoniae pose a very serious problem because of the production of extended-spectrum beta-lactamases which confer resistance to third generation cephalosporins. The percentage of ampicillin resistant E. coli among hospital isolates has rosen to 78% in U.S.A. nowadays. Recently, the emergence of E. coli strain resistant to combination of amoxycillin and clavulanate, due to hyperproduction of TEM-1 beta-lactamase, was observed. Inducible beta-lactamases mediate beta-lactam resistance in Pseudomonas aeruginosa which often develops during therapy of P. aeruginosa infections. Imipenem resistance is increasingly prevalent among P. aeruginosa isolates nowadays, but can be detected in K. pneumoniae due to the production of novel beta-lactamases and changes in outer membrane proteins.