ZIP (ZRT/IRT-like Protein) and CDF (Cation Diffusion Facilitator) are two large metal transporter families mainly transporting zinc into and out of the cytosol.Several ZIP and CDF transporters have been characterized in mammals and various model organisms, such as yeast, nematode, fruit fly, and zebrafish, and many candidate genes have been identified by genome projects. Unexpected functions of ZIP and CDF transporters have been recently reported in some model organisms,leading to major advances in our understanding of the functions of mammalian counterparts. Here, we review the recent information on the sequence similarity and functional relationship among eukaryotic ZIP and CDF transporters obtained from the representative model organisms.