The advent of more sophisticated studies published has clarified the 
understating of the root cause of various skin cancers or basal cell carcinomas 
(BCCs). The remarkable role is played by the comprehensive work done on 
unraveling the mechanism controlling the function of hedgehog (Hh) pathway. The 
defective Hh pathway has been found as the major cause for BCCs as activated Hh 
signaling within primary cilia plays a key role in the pathogenesis of BCCs. The 
BCC accounts for up to 40% of all cancers in the US, with growing incidences in 
other countries as well. Thus, it is considered to be utmost important by the 
researchers all over the world developing drugs for the treatment of skin 
cancers targeting Hh pathway. Fewer drugs like vismodegib, itraconazole and 
sonidegib have shown promising results inhibiting the awry function of Hh 
pathway resulting in treatment of different forms of skin cancers. These drugs 
have shown positive results but failed to prove their potential as expected. 
Vismodegib and sonidegib are better but fail in case of resistant tumors. This 
review article describes the mechanism of actions of these Hh pathway inhibitors 
and provides the rationale for their effectiveness/non-effectiveness for the 
treatment of metastatic or locally advanced BCC.