Five percent of patients with cutaneous squamous cell carcinoma develop locally advanced or metastatic disease that is not amenable to definitive surgical or radiation therapy. Cemiplimab, an antibody against programmed death receptor-1, was approved in the United States for the treatment of locally advanced and metastatic cutaneous squamous cell carcinoma in 2018. We performed a literature review on the use of cemiplimab in cutaneous squamous cell carcinoma, with an emphasis on efficacy, safety and tolerability, patient selection, and future directions. Embase and PubMed were searched for relevant terms, and 23 peer-reviewed journal articles presenting primary data on cemiplimab treatment in 5 or more subjects with cutaneous squamous cell carcinoma were included and summarized. Objective response rates in locally advanced and metastatic disease ranged from 42.9% to 50.8% in Phase I/II clinical trials and 32-77% (median 58%) in post-approval observational studies. Phase II trials looking at neoadjuvant use also had favorable response rates. Real-world studies demonstrated cemiplimab efficacy in periorbital tumors, tumors with large caliber perineural invasion, and tumors in solid organ transplant recipients. Cemiplimab was safe and well-tolerated in most patients. While side effects such as fatigue, diarrhea, pruritus, and rash were fairly common, only 9.8% of adverse events required cessation of therapy in phase II trials. Severe adverse events were primarily immune-mediated, including pneumonitis, myocarditis, myositis, and autoimmune hepatitis; the risk of treatment-related death was 3% in clinical trials. Further research on cemiplimab therapy in cutaneous squamous cell carcinoma is needed, and trials are now underway to obtain Phase IV long-term real-world data, further data on adjuvant and neoadjuvant use, and additional data in special populations such as stem cell and solid organ transplant recipients.