Members of the T-box gene family (Tbx) are essential for normal heart development, and mutations in human TBX genes cause congenital cardiovascular malformations. T-box genes have been implicated in early cardiac lineage determination, chamber specification, valvuloseptal development, and diversification of the specialized conduction system in vertebrate embryos. These genes include Tbx1, Tbx2, Tbx3, Tbx5, Tbx18, and Tbx20, all of which exhibit complex temporal spatial regulation in developing cardiac structures. Less is known about T-box genes in invertebrate heart development, but multiple T-box genes are expressed in Drosophila cardiac lineages. The molecular hierarchies and developmental processes controlled by T-box genes in the heart are the focus of this review.