Background: Gradenigo’s syndrome is an uncommon triad of retroorbital pain, diplopia due to 6th nerve palsy, and otorrhea due to otitis media and petrous apicitis. Although rarer in the antibiotic era, this syndrome may be life-threatening and highly morbid if not treated aggressively with IV antibiotics, and surgery in some cases. Methods and Findings: Herein we present a review of patients reported in the literature since 1990, with an exploration of medical vs. surgical treatment, causative organisms, and patient outcomes. Thirty-seven studies representing 38 patients were identified. The mortality rate was 2.6%, and the majority of patients were treated with either IV antibiotics alone (14) or IV antibiotics in addition to surgery (14). Conclusions: Prompt awareness of Gradenigo’s syndrome can help avoid morbidity or mortality related to this uncommon phenomenon. It should be kept in the differential of any patient with otitis media, retroorbital pain, and diplopia.