Bupropion is a very popular medication prescribed to millions of patients globally for depression (Wellbutrin, GlaxoSmithKline, Research Triangle Park, NC) as well as an aid in smoking cessation (Zyban, GlaxoSmithKline, Research Triangle Park, NC). It has been reported to have some common dermatologic side effects, such as pruritus, urticaria and serum-sickness like reaction. The authors report a case of bupropion-induced Stevens-Johnson syndrome (SJS) with a concomitant acute psoriatic exacerbation in a 56-year-old woman, who began taking bupropion for treatment of depression. While the United States (U.S.) prescribing information for bupropion does include SJS as a rare potential side effect, it does not mention worsening of psoriasis. Physicians should be aware of the potential life-threatening adverse effects of this commonly prescribed medication as well as the risk in patients with known psoriasis.