High-dose immunosuppression used in the treatment of pyoderma gangrenosum predisposes patients to opportunistic infections. A 66-year-old man presented with recalcitrant pyoderma gangrenosum in which the ulcer itself became infected with herpes simplex virus type 1. This patient was immunosuppressed with multiple agents including topical and oral corticosteroids, cyclosporin, mycophenolate mofetil, intravenous immunoglobulin and infliximab. However, the patient's ulcer continued to extend despite this. It was not until the presence of this virus was detected using polymerase chain reaction on a viral swab of the lesion and oral aciclovir was commenced that the ulcer began to heal. In addition, a fungal granuloma developed on this patient's left forearm as a complication of the potent immunosuppression, which was resolved following treatment with oral voriconazole.