The use of anti-vascular endothelial growth factor (VEGF) agents has led to a dramatic increase in the number of intravitreal injections. Endophthalmitis remains a rare but potentially vision-threatening complication of intravitreal injections. Recent large series have estimated this risk to be about one in 3,000 injections or less. Bevacizumab, which is generally prepared by a compounding pharmacy, is associated with additional risks of contamination. Although endophthalmitis cannot be prevented in all cases, certain risk reduction strategies have been proposed, including the use of an eyelid speculum, povidone iodine, avoidance of needle contact with the eyelid margin or eyelashes, and avoidance of routine post-injection antibiotics. Despite these precautions, some patients will develop endophthalmitis following intravitreal anti-VEGF injections, and outcomes may be poor despite prompt and appropriate therapy.