T-box transcription factor genes are widely conserved in metazoan development and widely involved in developmental processes. With the phase of T-box gene discovery winding down, the phase of transcriptional target discovery for T-box transcription factors is finally taking off and yielding rich rewards. Mutant phenotypes in mouse and zebrafish as well as morpholino studies in zebrafish have helped to link the T-box genes to a variety of signaling pathways through diverse target genes and feedback loops. Particularly in early mesoderm development, it is emerging that a network of T-box genes interacts with Wnt/beta-catenin and Notch/Delta signaling pathways, among others, to control the important processes of mesoderm specification, somite segmentation, and left/right body axis determination.