We propose rituximab as a first-line therapy for pemphigus vulgaris and steroid-dependent bullous pemphigoid with or without systemic steroids. A brief review of the literature substantiates the significant risk associated with the use of long term, high-dose prednisone, mycophenolate mofetil (MMF), and azathioprine. No head-to-head studies are available with respect to safety and efficacy of rituximab versus these therapies. When comparing the side effects of rituximab to MMF, both are found to be mild when used as monotherapy in dermatologic patients. The most severe side effects of rituximab include fatal infusion reactions and hypersensitivity, pancytopenia, infection and organ dysfunction. With MMF, malignancy, pancytopenia, infection, and organ dysfunction are the most concerning side effects. The frequencies of these observed adverse events are difficult to compare, but the side effect profiles of rituximab and MMF are clearly similar. Therefore, there is equipoise whether to use rituximab before rather than after MMF and/or systemic corticosteroids.