This paper presents a review of studies about insulin and insulin-like substances in prokaryotes, eukaryotes and fungi have been published over the last two decades, constituting an updating of our previous review (1988) which included references to invertebrate insulin or insulin-like substances both in uni- and pluricellular Monera, Protoctista, Fungii and Animal species. This present article reviews experiments and evidence obtained using modern techniques in the understanding of molecule evolution and behaviour, which confirm its very ancient molecular structure origin. The involvement of insulin-like and related material in signalling biological pathway and modulator effects is also reported.