Areas covered: This review discusses the potential of inhibiting the Wnt/beta beta-catenin signaling pathway, as a therapeutic approach for cancer, along with an overview of the development of specific inhibitors. Expert opinion: Cancer stem cells (CSCs) play a significant role in the development and recurrence of several cancers, and Wnt/beta beta-catenin signaling is important for the proliferation of CSCs. Inhibition of Wnt/beta beta-catenin signaling is therefore a promising treatment approach. Progress has been made in the development of screening methods to identify Wnt/beta beta-catenin signaling inhibitors. Biomarker-based screening is an effective and promising method for the identification of compounds of interest.