Efalizumab is one of the new biologic therapies targeting T-lymphocyte activity for the treatment of chronic plaque psoriasis. Common adverse effects include headaches, nonspecific infection, nausea, chills, and fever. Rebound of psoriasis following discontinuation of the drug has been reported. Relapse events can manifest as recurrent plaque psoriasis, guttate psoriasis, psoriatic erythroderma, and pustular psoriasis. We report a second case of withdrawal flare resulting in generalized pustular psoriasis.