We report two cases of adult males with sleep-related eating disorder (SRED), with durations of 3 and 7 years, and without associated psychiatric history. In both cases, the use of low-dose (25 mg) sertraline taken at bedtime resulted in immediate, full and sustained resolution of symptoms at the latest follow-ups. The sertraline efficacy was of particular benefit for the patient reported on in case 2 who was a commercial airline pilot subjected to a highly restricted list of Federal Aviation Administration-approved medications. Risk factors for SRED included smoking cessation and work-related stress in case 1, and a history of sleepwalking and work-related circadian disruptions and partial sleep deprivations in case 2. Sertraline therapy of SRED is considered within a review of all current pharmacologic therapies of SRED.