Postoperative endophthalmitis is a serious, vision-threatening complication of intraocular surgery. Better instrumentation, surgical techniques, prophylactic antibiotics and better understanding of asepsis have significantly reduced the incidence of this complication. Postoperative endophthalmitis may occur as an isolated event or as a cluster infection. Topical antibiotics, preoperative periocular preparation with povidone-iodine combined with a sterile operating room protocol significantly reduce the incidence of isolated postoperative endophthalmitis. The role of antibiotics in the irrigating fluid and subconjunctival antibiotics remains controversial. Cluster infections on the other hand are more likely to occur due to the use of contaminated fluids/viscoelastics or a breach in operating room asepsis. Prevention of postoperative endophthalmitis requires strict adherence to operating room norms, with all involved personnel discharging their assigned roles faithfully.