Abstract: Osteosarcoma is the most prevalent primary malignant bone tumor in children and teenagers with a poor survival in 40% of the victims.The Wnt/β-catenin signaling pathway has been shown to play a major role in bone cell differentiation, proliferation and apoptosis.It is a critical component of bone mass regulation and required for bone to respond to mechanical loading.The pathway is tightly regulated by a number of modulator proteins.Mutations in pathway components that result in aberrant regulation are involved in a number of bone diseases, especially Osteosarcoma.The use of Wnt pathway associated markers appear promising for osteosarcoma.Drugs targeting the Wnt pathway will gain even more attention.