Cemiplimab (Libtayo) is an antibody immunotherapy that stimulates an anti-cancer response via programmed cell death protein-1 (PD-1) blockade. It is the first approved treatment in the USA and EU for patients with locally advanced (laCSCC) or metastatic (mCSCC) cutaneous squamous cell carcinoma who are not candidates for curative surgery or curative radiotherapy. Approval was based largely on positive results from the phase II EMPOWER-CSCC 1 trial in this patient population. In this pivotal trial, treatment with intravenous cemiplimab 3 mg/kg once every 2 weeks or 350 mg once every 3 weeks resulted in a clinically significant objective response rate across laCSCC and mCSCC patient groups. Furthermore, responses appear to be durable, as the median duration of response has not yet been reached. Similarly, the median overall survival has also not yet been reached as of the latest data cut-off date. The safety and tolerability profile of cemiplimab was acceptable, with most immune-related adverse events being clinically manageable with appropriate therapy or discontinuation of cemiplimab. Overall, cemiplimab has a durable, clinically significant effect and an acceptable tolerability and safety profile. As the first approved treatment for this indication, cemiplimab represents a welcome therapeutic advance for patients with advanced CSCC.