Wnts are a family of secreted glycoproteins that act as ligands to activate receptor-mediated signaling pathways. The first described Wnt pathway, and the best understood, is one that works through a cytoplasmic protein, β-catenin. Specific members of the Wnt family interact with a Frizzled receptor complex, promoting the activity of Dishevelled, which in turn enhances the stability and activity of β-catenin. β-catenin probably binds members of the T cell factor and lymphoid enhancer factor (TCF/LEF) family of transcription factors, or to various other proteins, to regulate expression of target genes in a cellular context-dependent manner. Wnt signaling through this pathway regulates cell proliferation, survival, and cell fate. Inappropriate activation of this pathway may be an initiating event in some cancers, and inhibiting this pathway in transformed cells shows promise for anticancer therapies. Conversely, activation of this pathway shows promise as a target for developing osteoporosis, neurodegenerative disease, and stem cell therapies. The Connections Map for this Pathway provides an overview of the many signals that converge on β-catenin and influence Wnt signaling.