Less than 40% of depressed older adults treated with an antidepressant achieve remission. Incomplete response to treatment is common. Current augmentation strategies have limited efficacy, and many have side effects that restrict their utilization in older adults. We conducted the first open pilot trial of minocycline augmentation in older adults who had failed to achieve remission after adequate psychopharmacologic treatment. Subjects older than 55 years of age with major depression and failure to achieve substantial improvement of depressive symptoms after at least 6 weeks of antidepressant treatment were given augmentation with minocycline 100 mg twice daily over an 8-week period. At the end of 8 weeks of augmentation with minocycline, 31% (4/13) patients achieved remission. Remitters had higher baseline ratings of hopelessness and apathy. Minocycline was well tolerated with no reported adverse events or discontinuation due to intolerance. Larger placebo-controlled studies are needed to evaluate the effects of minocycline augmentation in older adults who had failed to achieve remission after adequate treatment with antidepressants.