The Wnt/beta-catenin signaling pathway plays crucial roles in various biological processes, including; cell proliferation and differentiation, regulation of cell cycle, cell-cell and cell-matrix interactions, angiogenesis, apoptosis and adipogenesis. The Wnt/beta-catenin signaling pathway starts with the binding of the Wnt protein to its cell surface receptors, and an extracellular signal is transferred to the cytoplasm and nucleus from the cell membrane. Transcription of various genes is activated by the activation of the signaling pathway in the nucleus. However, mutations of genes, which encode Wnts, Fz and LRP5/6 proteins, may cause aberrant activation of Wnt/beta-catenin signaling and also many severe diseases, especially cancer. Therefore, clarifying this pathway and its biomolecules is quite important for determining both the etiologies of the diseases, and novel target molecules that can be used for treatment. Thus, we aimed to discuss the initial step of the Wnt/beta-catenin signaling mechanism on the target cell membrane, and biomolecules such as Wnt, Fz and LRP5/6 involved in this mechanism, and in this manner we intended to clarify fully the signaling mechanism.