Rosacea is a chronic inflammatory skin condition that usually affects the central portion of the face. Pharmacologic interventions range from topical to systemic medications, with the ideal choice dependent on the symptoms and severity of each individual patient. Despite this variety of therapeutic options, none of these therapies are completely curative, and further researches are required in order to create more targeted and effective treatment strategies. Recent reports demonstrate botulinum toxin can provide symptomatic relief of severe facial flushing with corresponding decreases in cutaneous blood flow by working as a neuromodulator. Moreover, tacrolimus, topical calcineurin inhibitor, suppresses T cell activation and prevents further release of inflammatory cytokines related to a pathogenesis of rosacea. 595-nm pulsed-dye laser (PDL) is also known to be effective at treating facial telangiectasia and erythema due to its target to the oxyhemoglobin in the cutaneous vasculature. Herein, we report several cases of refractory rosacea successfully treated with botulinum toxin and combination of tacrolimus and 595-nm PDL.