Guidelines and treatment strategies for the new biological agents have been developed, but dermatologists continue to face difficulties in adopting these guidelines into their daily practices. We report a patient with psoriasis and psoriatic arthritis whose skin lesions responded only to efalizumab, and the arthritis to etanercept. This case shows that different biological agents may achieve different success rates even in the same patient. Each biological agent offers different advantages and disadvantages, which sometimes make it difficult to choose the single best agent for a patient. Psoriasis often becomes one of the most difficult diseases to treat and does not respond to any single antipsoriatic agent. Perhaps in the future, rotational or combination treatment with different biological treatments will be used.