We compare 4 cases of postoperative endophthalmitis due to trypan blue contaminated with Pseudomonas aeruginosa and Burkholderia cepacia and review the literature of gram-negative endophthalmitis. Two cases were due to P. aeruginosa with rapid onset, fulminate course, and loss of vision despite systemic and intravitreal antibiotics. Two cases due to B. cepacia had delayed presentations and were diagnosed on days 23 and 27. Burkholderia cepacia was difficult to treat, requiring multiple courses of antibiotics and ophthalmologic procedures. Outcomes were poor for all 4 patients: 2 required enucleation, 3 had permanent loss of vision, and 1 was left with visual acuity to hand movements. The contrasting clinical presentations and difficulties with diagnosis and treatment of gram-negative endophthalmitis caused by these 2 organisms are compared with other cases in a review of the literature. These cases highlight the serious nature of gram-negative endophthalmitis and the need for better treatment strategies.