Pemphigus vulgaris is a blister-forming autoimmune disease that causes an increased risk of irritation and infection due to the skin barrier disruption in the area of the blisters. We report about a 62-year-old patient with pronounced oral mucosa and skin manifestations of a pemphigus vulgaris which did not regress after initial therapy with high doses of prednisolone and steroid-saving immunosuppressants. The severe course of the disease was further complicated by occurrence of a sepsis, which had to be treated in an intensive care unit. By administration of rituximab and accompanying immunapheresis treatment, we achieved a partial remission after 8 months and a complete remission after 1.5 years. Pemphigus vulgaris is still a severe skin disease with a lot of complications that can be a therapeutic challenge.