Escherichia coli and Klebsiella pneumoniae are two important members of Enterobacteriaceae family. They are involved in sever community and hospital acquired infections such as urinary tract infections (UTIs), gastroenteritis, and pneumonia. Some of these diseases are associated with high mortality rates if not treated properly, so it is important to combat them with highly effective antibiotics. The most commonly used antimicrobial agents are beta-lactams such as penicillins, cephalosporins and other non-beta lactams such as aminoglycosides and quinolones. Extensive use of antimicrobials and disinfectants has promoted the rapid development of bacterial resistance. This bacterial resistance becomes a global health problem especially in developing countries. The increased rate of resistance towards different classes of antibiotics limits the treatment options for such infections. The antibacterial activity of some antimicrobial agents can be enhanced by the addition of new β-lactamase inhibitors. Further in vivo investigation is needed to confirm their therapeutic efficacy against local isolates.