Nonmelanoma skin cancer (NMSC) is the most common cancer in patients and 
includes basal cell carcinoma (BCC) and squamous cell carcinoma (SCC). 
Treatments useful for SCC and BCC include surgical, topical, and in advanced 
cases systemic chemo-radiation. This review of the literature aims to describe 
previous and current treatment options for oral therapy in locally advanced and 
metastatic NMSC otherwise unamenable to standard treatment. Oral Smoothened 
(Smo) inhibitors Vismodegib, Sonidegib, and Taladegib have shown to be effective 
in several trials. Oral tyrosine kinase inhibitors Erlotinib and Gefitinib, 
which target epidermal growth factor receptor (EGFR), have early supporting data 
and are currently undergoing large multicenter trials. Other less studied oral 
therapies which have shown at least partial efficacy include 5-Fluorouracil, 
capecitabine, and picropodophyllin. In vitro studies have elucidated new targets 
for dual combination oral therapy targeting both EGFR and insulin-like growth 
factor 1 receptor (IGF-1R). It is important to stratify treatment options based 
on patient risk of advanced disease, failure of conservative treatment, and 
ill-tolerated intravenous chemotherapy adverse events. Oral therapy in NMSC is 
useful in high risk patients with recurrent and aggressive disease who may not 
tolerate other systemic therapies.