Members of the Btg/Tob protein family share a conserved N-terminal region that confers the activity to inhibit cell proliferation. Tob1 and Tob2 proteins, which constitute a Tob subfamily, have a longer C-terminal region than BTG proteins. Apparently, genomes of invertebrates and teleost species contain only a single Tob locus, whereas genomes of mammalian, avian, and amphibian species contain two Tob loci (Tob1 and Tob2). Tob genes are expressed in oocytes, sperm, early embryos, and various adult tissues, depending on the species. Recent reports indicate that Tob proteins play important roles in spermatogenesis, embryonic dorsoventral patterning, osteogenesis, T-cell activation, and learning and memory. Accumulating evidence supports the hypothesis that Tob proteins act primarily as transcriptional repressors in several signaling pathways. Developmental Dynamics 236:913–921, 2007. © 2007 Wiley-Liss, Inc.