Endophthalmitis following penetrating eye injuries has a relatively poor prognosis due to the underlying eye trauma and the frequency of more virulent organisms such as Bacillus species. Risk factors for infection include 1) retained intraocular foreign body, 2) a rural injury setting, 3) delay in primary wound closure, and 4) disruption of the crystalline lens. Although endophthalmitis is difficult to distinguish from traumatic changes, recognition of early clinical signs of endophthalmitis, such as hypopyon, vitritis, or retinal periphlebitis, is important and early treatment is recommended. Comprehensive prophylactic antibiotic treatment at the time of injury repair combined with timely diagnostic vitrectomy and injection of intravitreal antibiotics when infection is suspected may significantly improve visual acuity outcomes following penetrating injuries. Treatment includes intravitreal, periocular, and systemic antibiotics. Intravitreal and periocular corticosteroids are also recommended. Recent and past literature supporting these recommendations, as well as the authors' specific prevention and treatment protocols for post-traumatic endophthalmitis, is included in this review.