Anal squamous cell carcinoma (SCCA), among other malignancies, is associated with the human papillomavirus (HPV) and its incidence continues to rise. Anal SCCA will likely remain an existing healthcare concern given compliance issues with the HPV vaccination seen in the US. Localized disease is predominantly treated with standard of care (SOC) definitive chemoradiation that has remained unchanged for decades. Clinical and molecular prognostic factors have emerged to characterize patients unresponsive to SOC, revealing the need for an alternate approach. Metastatic disease is an extremely small subset and understudied population due to its rarity. Recent prospective trials and mutational analysis have opened treatment options for this subset in need. Our review details the pharmacotherapeutic treatment in localized and metastatic anal SCCA chronologically, while also describing future outlooks.