Pemphigus is a rare autoimmune disease characterized by flaccid blisters and erosions on skin and mucous epithelia. A critical event in its pathogenesis is production of antidesmoglein antibodies, which mediate the loss of intercellular adhesion in epithelia, leading to blister formation. Multiple environmental factors (ultraviolet radiation, trauma, drugs, infective agents) have been suggested as possible triggers of pemphigus. Occasionally, the disease has been reported to follow viral and bacterial vaccination. We describe a patient who experienced exacerbation of pemphigus shortly after administration of the influenza vaccination on two separate occasions. We review the literature, suggest possible explanations for a causal relationship, and discuss the administration of vaccination to these patients.