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Bacterial infections are very commonly acquired infections. Cephalosporins are broad-spectrum antibiotics used to manage a wide-variety of infections caused by gram-positive and gram-negative bacteria. The knowledge of the basic chemistry helps in understanding the pharmacokinetic, antimicrobial and toxicological profiles of cephalosporins. Cephalosporins are antibiotics with bactericidal activity which act by inhibiting the synthesis of cell wall in bacteria. The drugs of this class are classified into five generations in which the antimicrobial spectrum shifts from gram-positive bacteria to gram-negative bacteria with increasing generations of Cephalosporins. Antibiotic-producing bacteria contain a wide range of complex defense mechanisms to protect themselves from their own antibiotics and it results in the development of antibiotic resistance. The various mechanisms by which bacteria develop resistance are: production of β-lactamases, alteration of the porin channels, alteration of molecular structure of transpeptidase, and upregulation of cephalosporin efflux pumps. The new cephalosporins are the foundation for the real warning signs to open up new and interesting possibilities for serious infections in the future thereby ensuring rational selection of antibiotics for various infections.