Endophthalmitis is an uncommon but potentially devastating intraocular infection that can occur after routine cataract surgery. Although a broad spectrum of organisms have been shown to cause acute postoperative endophthalmitis, most cases are caused by Gram-positive bacteria, which may be introduced at the time of surgery from colonization of adjacent conjunctiva or eyelid skin. Risk factors for the development of endophthalmitis following cataract surgery include patient age, intraoperative surgical complications and poor wound construction. There are several antibacterial strategies employed to prevent postoperative endophthalmitis, with topical, intracameral and subconjunctival delivery being the most common. Worldwide, there seems to be significant regional variance in the type and method of prophylactic antibacterial regimens; for example, topical fluoroquinolones are commonly used in the US, while intracameral cephalosporins are employed widely in Europe. The optimal antibacterial strategy for the prevention of endophthalmitis should be safe, inexpensive and broad in microbiological activity spectrum, while not requiring patient compliance for its effectiveness.