Medullary thyroid cancer (MTC) is a prototypic neuroendocrine tumor of the thyroid C cells. Other than surgery, there are no curative therapies for MTC. In this review, we detail recent studies that suggest that targeting specific signaling pathways may be a viable strategy to control MTC tumor progression. Specifically, we discuss the role of the raf-1 and achaete-scute homologue-1 pathways in the MTC tumor growth and differentiation.