Post-traumatic endophthalmitis is an uncommon yet devastating complication of an open globe injury. Risk factors include presence of an intraocular foreign body (IOFB), lens rupture, delayed primary globe repair, rural trauma, and trauma with contaminated objects. Visual prognosis in post-traumatic endophthalmitis is affected by the virulence of the microbe, the presence of a retinal break or detachment, the timing of treatment, the presence or absence of an IOFB, and the extent of initial injury. Treatment should be started emergently with systemic and intravitreal antibiotics. In the setting of penetrating ocular trauma, antibiotic prophylaxis of endophthalmitis should be considered. The best treatment regimen has not been determined. The most frequent prophylactic regimens are: treatment with oral antibiotics, a short course of intravenous antibiotics followed by oral antibiotics, or intravitreal antibiotics plus oral antibiotics.