Psoriasis is a common dermatosis affecting the skin, mucosal surfaces, and cutaneous adnexa, and joints and bones can be involved at some degree in the clinical features of the disease, configuring psoriatic arthritis. Moderate to severe psoriasis has a high impact on quality of life and requires an integrated and long-term treatment schedule. However, management of psoriasis in patients affected by other systemic diseases can be challenging because of the possible side effects or contraindications of various treatments in accordance with patients' medical history. In recent times, the therapeutical approaches have changed a lot, thanks to biologicals. The current authors present some cases of psoriatic patients with comorbidities successfully treated with efalizumab, an anti-T lymphocyte biological.