In recent years, informatics studies have predicted several new ways in which the transforming growth factor beta (TGFbeta) signaling pathway can be post-translationally regulated. Subsequently, many of these predictions were experimentally validated. These approaches include phylogenetic predictions for the phosphorylation, sumoylation and ubiquitylation of pathway components, as well as kinetic models of endocytosis, phosphorylation and nucleo-cytoplasmic shuttling. We review these studies and provide a brief ;how to' guide for phylogenetics. Our hope is to stimulate experimental tests of informatics-based predictions for TGFbeta signaling, as well as for other signaling pathways, and to expand the number of developmental pathways that are being analyzed computationally.