Many eukaryotic proteins bind to membranes using a glycosylphosphatidylinositol (GPI) anchor. GPI anchors are essential in yeasts and probably also in protozoa. Although mammalian cells can survive without GPI anchors, their deficiency in haemopoietic cells cause a haemolytic disease, paroxysmal nocturnal haemoglobinuria (PNH). Here, we discuss recent progress in our understanding of GPI-anchor biosynthesis that could lead to a better understanding of PNH and chemotherapeutic agents to treat protozoal and fungal infections.