The Hedgehog signaling pathway plays a key role in directing growth and patterning during embryonic development and is required in vertebrates for the normal development of many structures, including the axial skeleton, neural tube, lungs, hair, and teeth. Recent evidence has implicated a pathologic role for the Hh signaling pathway in the development of the common skin cancer, basal cell carcinoma (BCC). This chapter provides an overview of the biology and molecular genetics of BCCs and reviews the mechanisms by which activation of Hh signaling may lead to the development of this common cancer.