Wnt-1 was first identified as a proto-oncogene activated in mouse mammary tumors induced by mouse mammary tumor virus in 1982. Wnt-1 signal is a secreted glycoprotein that plays important roles in embryonic development and carcinogenesis. In a conditional Wnt-1 transgenic mouse tumor model, reduction of Wnt-1 signaling results in the regression of the Wnt-1 initiated primary mammary tumors and lung metastasis. Aberrant activation of the Wnt pathway has been strongly linked to the development of human cancers. Increased Wnt-1 signal has been found in a variety of human cancers. Our group has shown that blockade of Wnt-1 signaling, by either Wnt-1 small interference RNA or anti-Wnt-1 antibody induces apoptosis in human cancer cells and inhibits tumor growth in vivo. This review summarizes the recent significant findings and the potentials of Wnt-1 signal as a new therapeutic target for cancer.