Anti-inflammatory dose doxycycline (ADD), which is the administration of doxycycline 40 mg extended-release capsule once daily, is the only oral therapy approved by the United States Food and Drug Administration (FDA) for treatment of rosacea. ADD once daily has been shown to exhibit anti-inflammatory activity while not demonstrating evidence of antibiotic effects, including with chronic administration. This article summarizes the clinical studies to date on the use of ADD once daily in papulopustular rosacea, including both monotherapy and combination therapy studies. The combination therapy approach of ADD once daily and metronidazole gel 1% once daily has been shown to exhibit a more rapid onset of therapeutic effect than topical therapy alone. ADD once daily has been demonstrated to be effective in adult subjects with moderate to severe rosacea, and exhibits a favorable safety profile coupled with absence of antibiotic selection pressure. Additionally, a much lower incidence of gastrointestinal side effects has been noted with ADD once daily as compared to doxycycline 100 mg once daily.