Methotrexate, the most common systemic small molecule used in the treatment of moderate to severe psoriasis, is associated with significant toxicities and adverse events. Long-term continuous usage is not recommended due to potential liver toxicity, myelosuppression, and other side effects. Abrupt cessation of methotrexate without tapering can lead to flare-up and rebound of psoriasis. Here we describe sustained clinical responses in 6 patients with psoriasis following gradual cessation of methotrexate through the addition of etanercept therapy.