Glypicans are a family of heparan sulfate proteoglycans that are attached to the outer plasma membrane leaflet of the producing cell by a glycosylphosphatidylinositol anchor. Glypicans are involved in the regulation of many signalling pathways, including those that regulate the activities of Wnts, Hedgehog (Hh), Fibroblast Growth Factors (FGFs) and Bone Morphogenetic Proteins (BMPs), among others. In the Hh signalling pathway, glypicans have been shown to be essential for ligand transport and the formation of Hh gradients over long distances, for the maintenance of Hh levels in the extracellular matrix and for its unimpaired reception in distant recipient cells. Recently, two mechanistic models have been proposed to explain how Hh can form the signalling gradient and how glypicans may contribute to it. In this review, we describe the structure, biochemistry and metabolism of glypicans and their interactions with different components of the Hh signalling pathway that are important for the release, transport and reception of Hh.