Cutaneous squamous cell carcinoma (cSCC) is the second most common skin cancer after basal cell carcinoma (BCC). The incidence of cSCC in the United States and throughout the world is increasing. In the US, each year 200,000-400,000 new cases of cSCC are expected, with disease-related death occurring in more than 3,000 people with cSCC. Most patients with cSCC are cured with surgery, however, in some patients these tumors can become metastatic or locally advanced and are not cured by surgery or radiation therapy. A large follow-up study of the US population showed that the incidence of invasive cSCC, which may advance or metastasize, increased during an 18-year follow up period. Advanced cSCC is a life-threatening condition, and currently no systemic therapies are approved. Recently, immune checkpoint inhibitors that block the PD-1/PD-L1 pathway have shown promise in the treatment of advanced cSCC. Dermatologists play an important role in the management of cSCC, and their awareness about recent developments in risk stratification, targeted therapies, and follow-up for patients with advanced cSCC is crucial to improve prognosis.