The Wnt signaling pathways play fundamental roles in the differentiation, proliferation, death and function of many cells and as a result are involved in critical developmental, growth and homeostatic processes in animals. There are four currently known pathways of Wnt signaling; the so-called canonical or Wnt/beta-catenin pathway, the Wnt/Ca(+2) pathway involving Protein Kinase A, the planar cell polarity pathway and a pathway involving Protein Kinase C that functions in muscle myogenesis. The best studied of these is the Wnt/beta-catenin pathway. The Wnts are an evolutionarily highly conserved family of genes/proteins. Control of the Wnt pathways is modulated by a number of the proteins that either interact with the Wnt ligands directly, or with the low density lipoprotein-receptor related proteins (LRP) 5 and 6 that along with one of several Frizzled proteins function as co-receptors for the Wnt ligands. Aberrant regulation resulting as a consequence of mutations in any of several components of the Wnt pathway and/or protein modulators of the pathway have been shown to cause a wide spectrum of diseases. This review will briefly touch on various diseases of Wnt signaling including cancer, aortic valve calcification and several bone related phenotypes. Our emerging understanding of Wnt signaling offers great hope that new molecular based screening tests and pharmaceutical agents that selectively target this pathway will be developed to diagnose and treat these diseases in the future.