Post-tympanostomy tube otorrhea is a common problem that is treated by both primary care physicians and otolaryngologists. Physicians should take a logical approach to managing this condition in order to prevent the development of antimicrobial resistance and to minimize healthcare expenditures. Once the diagnosis has been made, first-line therapy with fluoroquinolone drops, with or without suctioning, is preferred. If the condition does not resolve after a few days, suctioning is recommended and oral antimicrobial therapy can be initiated, depending on the clinical situation. Parenteral therapy is sometimes necessary for those very few patients who do not improve with oral and topical antimicrobial therapy and aggressive local care. The use of prophylactic drug therapy is controversial.