The therapeutic activity of antibiotics depends on several factors including absorption, elimination kinetics, distribution in the body, minimal inhibitory concentrations (MIC), stability against enzymes, and plasma-protein binding. Some of these factors are interrelated, for example, the extent of protein binding of an antibiotic influences its elimination kinetics, distribution into tissues, MIC, and antibacterial activity. To evaluate the potential efficacy of an antibiotic, it is important to know the extent of its binding to plasma proteins especially since the protein-bound fraction of the antibiotic is devoid of antibacterial activity. Cephalosporins are a new class of broad-spectrum antibiotics that bind to plasma proteins in different degrees. Reported values for protein binding range from 6% for cephradine to 92% for cefazolin. The effects of protein binding of some of the commonly used cephalosporins on antibacterial activity and several pharmacokinetic parameters are discussed in this communication.