Over the past two decades, a huge progress in the treatment of psoriasis was achieved by targeting the human cytokine network. At present, 11 biologicals – antibodies, and a soluble receptor – are used to neutralize key inflammatory cytokines. Based on their targets, they can be grouped into the following four classes: TNF-α-, IL-12/23-, IL-17- and IL-23-inhibitors. The number of substances, but also the different modes of action may be challenging, when selecting the right drug for an individual patient. In this article, we provide an overview of the available biologicals in the treatment of psoriasis, including their advantages and limitations, and summarize criteria for therapy selection.