Metallothioneins (MTs) are a class of ubiquitously occurring low molecular weight cysteine- and metal-rich proteins containing sulfur-based metal clusters. The conservation of these clusters in an increasing number of three-dimensional structures of invertebrate, vertebrate and bacterial MTs signifies the importance of this structural motif. In the postgenomic era, it is becoming increasingly clear that MTs fulfil different functions. Increasing body of evidence show that diverse functions of the mammalian MT-1/MT-2 isoforms including involvement in zinc homeostasis, protection against heavy metal toxicity and oxidative damage are related to their clusters. In contrast, the biological properties of the brain-specific MT-3 isoform imply that the clusters in this protein play a structural role. The recent highlights of MT research are the subject of this review.