Recent approval and marketization of novel treatments have widened the range of therapeutic opportunities for moderate-to-severe psoriasis. In the next years, this panorama will be further enlarged as many other agents, both oral small molecules and biologics, have passed phase III and are expected to be approved, and subsequently marketed, shortly. In spite of this array of therapeutic possibilities, there is still an unmet need for an appropriate treatment in a large number of cases. This review was aimed to describe general principles regarding the therapeutic approach to moderate-severe plaque psoriasis, providing an updated overview of the therapeutic armamentarium that is specifically available in Italy, drug prescriptibility, and some peculiar limitations for reimbursement defined by our National Health Care System.