The treatment of advanced basal cell carcinoma (BCC) often requires therapies beyond local surgical excision or radiation due to the invasiveness of the tumor. Historically, cytotoxic chemotherapy was used to treat advanced BCC, but with limited data, no standard regimens were established. The discovery of cyclopamine, a natural inhibitor in the Hedgehog pathway, led to the development of the 2 currently approved Hedgehog inhibitors, vismodegib and sonidegib. Both agents are indicated for locally advanced BCC, while vismodegib is also indicated for metastatic BCC. In patients who progress on hedgehog inhibitors or cannot tolerate hedgehog inhibitors, the programmed cell death protein 1 inhibitor cemiplimab can be used to treat locally advanced or metastatic disease. Complex cases of locally advanced or metastatic BCC may be best discussed through a multidisciplinary approach in order to determine the optimal treatment approach for the individual patient.