Psoriasis is a chronic, inflammatory, hyperproliferative skin disease that affects 1-2% of the general population in the UK and US. Plaque psoriasis is the most common form, accounting for approximately 90% of cases. The disease is usually chronic and persistent, although up to 50% of patients may enter spontaneous remission for varying periods of time. There is no cure for psoriasis; therefore, the aim of treatment is to minimize the extent and severity of the disease to the point at which it no longer substantially disrupts the patient's quality of life. First-line therapy of psoriasis usually consists of topical agents, such as emollients, tar, dithranol, and vitamin D3 analogs. In cases of severe, extensive psoriasis, where topical therapy is either impractical or not sufficiently effective, systemic treatment may be warranted at the outset. In these circumstances, the therapeutic options include: (i) intensive inpatient or day center topical therapy; (ii) phototherapy; and/or (iii) systemic agents. There are now a number of systemic agents available for the treatment of severe psoriasis, but all have potential adverse effects. We review the current treatment options, which include the use of phototherapy and systemic agents, and provide recommendations on their use in clinical practice. Importantly, treatment should be tailored to each individual patient depending on concurrent medical problems (which might preclude certain agents), patient choice and acceptance of the risk of adverse effects.