Antimicrobial resistance is a natural biological phenomenon of response of microbes to the selective pressure of an antimicrobial drug. Resistance may be inherent, which explains the phenomenon of opportunistic infection or acquired. Concern about the resistance increased in the late 1990's and since then, many governmental and agency reports have been published regarding the agricultural use of antibacterials, advising less use of antibacterials, appropriate choice of antibacterials and regimens, prevention of cross-infection and development of new antibacterials. The emergence of multidrug resistant strains of Gram-negative bacteria (Pseudomonas, Klebsiella, Enterobacter, Acinetobacter, Salmonella species) and Gram-positive organisms (Staphylococcus, Enterococcus, Streptococcus species) is the more worrisome in the present therapeutic scenario. Multidrug - resistant tuberculosis is another serious public health problems. Resistance to some agents can be overcome by modifying the dosage regimens (e.g., using high-dose therapy) or inhibiting the resistance mechanism (e.g., beta-lactamase inhibitors), whereas other mechanisms of resistance can only be overcome by using an agent from a different class. It is urgently required to ban the sale of antibiotics without prescription, to use antibiotics more judiciously in hospitals by intensive teaching of the principles of the use of antibiotics and to establish better control measures for nosocomial infections. Thus, it is highly recommended that practicing physicians should become aware of the magnitude of existing problem of antibacterial resistance and help in fighting this deadly threat by rational prescribing.