Growth and lineage-specific differentiation constitute crucial phases in the development of stem cells. Control over these processes is exerted by particular elements of the extracellular matrix, which ultimately trigger a cascade of signals that regulate uncommitted cells, by modulating their survival and cell cycle progression, to shape developmental processes. Uncontrolled, constitutive activation of fibroblast growth factor receptors (FGFR) results in bone abnormalities, underlining the stringent control over fibroblast growth factor (FGF) activity that must be maintained for normal osteogenesis to proceed. Mounting evidence suggests that FGF signalling, together with a large number of other growth and adhesive factors, is controlled by the extracellular glycosaminoglycan sugar, heparan sulfate (HS). In this review, we focus on FGF activity during osteogenesis, their receptors, and the use of HS as a therapeutic adjuvant for bone repair.