Several of the nine hexahydroxycylohexanes (inositols) have functions in Biology, with myo -inositol (Ins) in most of the starring roles; and Ins polyphosphates are amongst the most abundant organic phosphate constituents on Earth. Many Archaea make Ins and use it as a component of diphytanyl membrane phospholipids and the thermoprotective solute di-L-Ins-1,1′-phosphate. Few bacteria make Ins or use it, other than as a carbon source. Those that do include hyperthermophilic Thermotogales (which also employ di-l-Ins-1,1′-phosphate) and actinomycetes such as Mycobacterium spp. (which use mycothiol, an inositol-containing thiol, as an intracellular redox reagent and have characteristic phosphatidylinositol-linked surface oligosaccharides). Bacteria acquired their Ins3 P synthases by lateral gene transfer from Archaea. Many eukaryotes, including stressed plants, insects, deep-sea animals and kidney tubule cells, adapt to environmental variation by making or accumulating diverse inositol derivatives as ‘compatible’ solutes. Eukaryotes use phosphatidylinositol derivatives for numerous roles in cell signalling and regulation and in protein anchoring at the cell surface. Remarkably, the diradylglycerol cores of archaeal and eukaryote/bacterial glycerophospholipids have mirror image configurations: sn -2,3 and sn -1,2 respectively. Multicellular animals and amoebozoans exhibit the greatest variety of functions for PtdIns derivatives, including the use of PtdIns(3,4,5) P 3 as a signal. Evolutionarily, it seems likely that (i) early archaeons first made myo -inositol approx. 3500 Ma (million years) ago; (ii) archeons brought inositol derivatives into early eukaryotes (approx. 2000 Ma?); (iii) soon thereafter, eukaryotes established ubiquitous functions for phosphoinositides in membrane trafficking and Ins polyphosphate synthesis; and (iv) since approx. 1000 Ma, further waves of functional diversification in amoebozoans and metazoans have introduced Ins(1,4,5) P 3 receptor Ca 2+ channels and the messenger role of PtdIns(3,4,5) P 3 .