The Clobex Spray Community-Based Research Assessment (COBRA) trial was a 4-week, open-label, observational, community-based trial that evaluated the use of twice-daily clobetasol propionate spray 0.05% either as monotherapy (n = 1254, effectiveness-evaluable [EE] population) or therapy added on to an existing regimen (n = 731, EE population) in subjects with moderate to severe plaque psoriasis. The key outcome measures were the change in target plaque severity (TPS) rating between weeks 0 (baseline) and 4 and the investigators' global assessment of improvement (GAI) rating at 4 weeks. This article focuses on clobetasol spray 0.05% when it is added to the 5 most commonly used treatment regimens in the COBRA trial add-on therapy group. Among the group of subjects receiving clobetasol propionate spray 0.05% as add-on therapy, the most common ongoing treatment was a biologic agent. The other more common ongoing treatments were topical calcipotriene, oral antipsoriatic agents, other topical corticosteroids (non-class 1), and topical calcipotriene plus other topical corticosteroids. Similar rates of treatment success (clear or almost clear) were seen in the subgroup analysis for each of the add-on regimens when assessed by both the TPS and GAI scales. On the TPS scale, success rates at week 4 were 76.0% to 84.0% for clobetasol propionate spray 0.05% added to biologic agents, topical calcipotriene, oral antipsoriatic agents, other topical corticosteroids, or topical calcipotriene plus other topical corticosteroids. It is notable that in subjects who were being treated with a variety of agents, the addition of clobetasol propionate spray 0.05% during the course of the study resulted in improvements in disease severity.