The rationale for prophylactic antibiotics in cataract operations must be continually reevaluated in light of cost-effectiveness and adverse reactions. The principles learned from wound infections associated with general surgical procedures should be applied to the limited knowledge about the rare event of endophthalmitis. Herein the literature on experimental and clinical wound infections in general surgical procedures is reviewed, with analysis of microbial flora, pathophysiology of wound infections, and pharmacokinetics of antibiotics. Experimental and clinical studies on prophylactic antibiotics to prevent endophthalmitis are reviewed, including information on topically applied antibiotics, chemical antisepsis, and administration of subconjunctival, intracameral, and systemic antibiotics. In addition, the benefits, limitations, and risks of the various types of prophylactic antibiotics are discussed. Because of the limited data on prophylactic antibiotics in cataract operations, providing dogmatic statements is difficult. General recommendations are offered based on the currently available literature, and a stratified approach is suggested based on wound construction and number of anterior segment maneuvers.