The WNT signaling cascade is integral in numerous biological processes including embryonic development, cell cycle regulation, inflammation, and cancer. Hyperactivation of WNT signaling secondary to alterations to varying nodes of the pathway have been identified in multiple tumor types. These alterations converge into increased tumorigenicity, sustained proliferation, and enhanced metastatic potential. This review seeks to evaluate the evidence supporting the WNT pathway in cancer, the therapeutic strategies in modulating this pathway, and potential challenges in drug development. Implications for Practice: The WNT signaling cascade is integral in numerous biological processes, including cell cycle regulation and cancer. Alterations in WNT signaling have been identified in numerous tumor types, and in recent years, numerous WNT pathway modulators have been tested in preclinical studies. These agents are now being investigated in the clinical arena, and this review describes the WNT pathway and therapeutics currently in development. The WNT signaling cascade is integral in numerous biological processes, including cell cycle regulation and cancer. Alterations in WNT signaling have been identified in numerous tumor types, and in recent years, numerous WNT pathway modulators have been tested in preclinical studies. These agents are now being investigated in the clinical arena, and this review describes the WNT pathway and therapeutics currently in development.