Cosibelimab (UNLOXCYT; cosibelimab-ipdl) is an anti-PD-L1 antibody developed by Checkpoint Therapeutics for the treatment of advanced cancers, including metastatic or locally advanced cutaneous squamous cell carcinoma (mCSCC or laCSCC). Cosibelimab is the first approved anti-PD-L1 therapy in the USA for the treatment of adults with mCSCC or laCSCC who are not candidates for curative surgery or curative radiation. In contrast to other anti-PD-L1 antibodies, cosibelimab can induce antibody-dependent cell mediated cytotoxicity as it includes a functional Fc domain. This article summarizes the milestones in the development of cosibelimab leading to this first approval for this indication.