Metastatic squamous cell anal carcinoma (SCAC) accounts for almost 500 deaths per year in the UK. The optimal first-line treatment for metastatic SCAC consists of combination chemotherapy, which provides only modest benefit with a short duration of response. Currently, there is no established second-line treatment for chemorefractory disease. Retifanlimab (a programmed cell death protein 1 inhibitor) has shown promise in patients with refractory, metastatic SCAC based on the POD1UM-202 study, and has potential in the first-line setting in combination with chemotherapy. This article will review the current treatment paradigms for SCAC, including the future use of immune checkpoint inhibitors, with a focus on retifanlimab in the treatment of SCAC.