ABSTRACT: Nail psoriasis affects 50% of psoriasis patients and in many cases causes impairment of manual dexterity, pain, and psychologic stress. Despite the fact that about 80% of psoriatic arthritis patients have nail involvement, patients rarely receive treatment for nail disease. Because of great difficulty in drug delivery to site of action and significant toxicities of most conventional systemic therapies, treatment of nail psoriasis can be very challenging. Biological therapy for psoriasis and psoriatic arthritis is now widely used, and early evidence indicates it may have significant benefit for some patients with psoriatic nail disease. This article reviews the clinical manifestations of nail psoriasis and discusses how to use specific biologic therapies that may provide significant new treatment options for this challenging disease.