WNT9 paralogues, WNT9A and WNT9B, are secreted ligands driving both the canonical (β-catenin dependent) and non-canonical (β-catenin independent) Wnt signaling pathways. These pathways play roles in cell fate determination, embryonic patterning, bone development, and organogenesis, among other biological processes. Studies of Wnt9a and Wnt9b mutant animals demonstrate that they have specific and overlapping roles in these processes. Wnt9a is critical in directing stem and progenitor cell fate during hematopoietic stem cell development, proper bone formation, and chondrogenesis, while Wnt9b is important for kidney and heart development. Both proteins are essential in craniofacial development and convergent extension movements. Dysregulated expression of human WNT9A and WNT9B have been implicated in different cancers and disease, suggesting these proteins or their downstream pathways may represent potential therapeutic targets.