Cephalosporins are the most commonly prescribed class of antibiotics, and its structure and pharmacology are similar to that of penicillin. It’s a bactericidal, and its structure contains beta-lactam ring, as like of penicillin, which intervenes in bacterial cell wall synthesis. Cephalosporins are derived from the mold Acremonium (previously called as Cephalosporium). It was first discovered in 1945; scientists have been improving the structure of cephalosporins to make it more effective against a wider range of bacteria. Whenever the structure of cephalosporins modified, a new ”generation” of cephalosporins are made. So far, there are five generations of cephalosporins available. They are prescribed against various organisms and infections. The cephalosporin antibiotics interfere with cell-wall synthesis of bacteria, leading to the breakdown of the infectious organism. To achieve this effect, the antibiotic must cross the bacterial cell wall and bind to the penicillin-binding proteins. Various generations of cephalosporins, mechanisms of resistance, pharmacokinetics, adverse reactions, and their clinical use were reviewed in this article. Most of the cephalosporins are available as parenteral, but the oral formulations are also available for certain drugs. Rather than learn all cephalosporins, it is reasonable for the clinician to be familiar with selected cephalosporins among the parenteral and oral formulations. © 2020 Elsevier B.V., All rights reserved.