Metallothioneins are metal-containing proteins that bind zinc, copper and other metallic ligands thanks to the cysteine residues of their polypeptide chain. In addition to supporting homeostatic buffering of metallic micronutrients into the cells by providing Zn and Cu supply, metallothioneins fulfil a broad range of other functions, including detoxification of toxic metals such as cadmium and mercury, scavenging of harmful reactive oxygen species, and others. Thus it is not surprising that the versatile metallothioneins are found from bacteria to fungi, protists, plants, and most animal groups. In spite of many studies on metallothioneins, little is known about their origin, evolution and diversification. This can be attributed to the lack of detailed comparative studies. Among vertebrates, a great deal of knowledge on metallothionein structure and function relies on studies carried out on mammalian metallothionein isoforms, followed by studies on piscine and avian metallothioneins, whereas very few data are available on reptilian and amphibian metallothioneins. To gain further insights into the history of this fascinating protein in vertebrates, we undertook a study about the expression, the function and the evolution of metallothionein gene(s) in reptiles. In this review, we summarize the results obtained studying the gene expression and the detoxification function of the metallothionein in embryonic and adult tissues of the lacertid Podarcis sicula and the evolution of the metallothionein gene in squamate reptiles.