Psoriasis is a common, chronic, immune-mediated, inflammatory skin disease with systemic involvement and significant impact on patients' quality of life. Several biologic treatments have been developed in recent decades, such as tumor necrosis factor (TNF)-α inhibitors, a non-selective interleukin (IL)-23 inhibitor (ustekinumab, which also inhibits IL-12), and-most recently-IL-17 inhibitors. Guselkumab is a novel biological therapy that selectively targets IL-23 and is the first-in-class selective IL-23 inhibitor approved to treat moderate-to-severe plaque psoriasis. These inhibitors are expected to have some advantages over the highly effective IL-17 inhibitors, as they do not worsen inflammatory bowel disease and are not involved in the development of candida infections. Additionally, selective inhibition of IL-23 may have additional benefits over ustekinumab as the IL-12-dependent cascades remain functional. These benefits include a decrease in IL-17A-producing T cells in the skin and the promotion of an anti-inflammatory effect through production of interferon-γ and IL-10. In terms of efficacy, guselkumab showed promising results in the treatment of psoriasis and psoriatic arthritis, although it did not show significant clinical improvement in rheumatoid arthritis. Studies in other inflammatory diseases and Crohn's disease are expected to begin soon. Overall, guselkumab was well tolerated; the most common adverse event was nasopharyngitis. Head-to-head studies comparing IL-23 inhibitors with agents in different classes, namely IL-17 inhibitors, will be crucial to establish the true role of these agents in psoriasis treatment.