BACKGROUND: Psoriasis is a chronic condition often managed with topical therapy. Patients have high expectations about the speed at which improvement is achieved, which then can have a marked impact on the patient's adherence to treatment. Recently, clinical data on a new fixed combination of halobetasol and tazarotene (HP/TAZ) have been presented. HP/TAZ lotion was statistically more effective than individual active ingredients or its vehicle, with a predictable safety profile. OBJECTIVES: Here we review the efficacy and tolerability data with a specific focus on the first two weeks of therapy. METHODS: Multicenter, randomized, double-blind, vehicle-controlled Phase 2 study in moderate or severe psoriasis (N=212). Subjects randomized (2:2:2:1 ratio) to receive halobetasol 0.01%/tazarotene 0.045% (HP/TAZ), individual active ingredients (HP or TAZ), or vehicle, once-daily for 8 weeks. Efficacy assessments included treatment success (defined as at least a 2-grade improvement from baseline in the IGA score and a score of 'clear' or 'almost clear'), and impact on individual signs of psoriasis (erythema, plaque elevation, and scaling) at the target lesion. RESULTS: As early as 2 weeks, HP/TAZ lotion demonstrated statistically significant superiority for treatment success over vehicle (P equals 0.047) and TAZ (P equals 0.029). By week 2, 47.5% of patients were 'mild', 'almost clear' or 'clear' compared with 33.3%, 16.9%, and 12.9% of patients treated with HP, TAZ, or vehicle, respectively; plaque elevation and scaling were significantly improved compared with HP, TAZ, or vehicle, and erythema was significantly improved compared with TAZ. Improvements in baseline itching (45.6%), dryness (42.2%), burning/stinging (55.9%) with HP/TAZ lotion at 2 weeks were similar to those seen with HP, and greater than that achieved with TAZ (30.8% [P equals 0.099], 35.4%, and 13.3%, respectively). CONCLUSION: The HP/TAZ fixed combination lotion provides rapid relief of psoriasis symptoms, with apparent benefits over both HP and TAZ by week 2. J Drugs Dermatol. 2018;17(8):863-868.