Preoperative or immediately postoperative antibiotics have been used by ophthalmic surgeons routinely as prophylaxis for postoperative endophthalmitis. The rationale for such prophylaxis, as the evidence which supports its efficacy are well founded. The optimal choice of antibiotics, however, from the standpoints of efficacy, delivery (route, dosage, and frequency of administration), adverse reactions, and cost is far less well established. This review considers these issues in the context of a critical evaluation of the pertinent literature.