The identification of the TGFbeta cytokine signaling pathway, including membrane receptor serine/threonine kinases and Smad transcription factors as their substrates, has allowed the delineation of a process for conversion of these signals into programs of gene activation and repression that underlie critical cell fate and developmental decisions. The deconstruction of one of these responses - the cell cycle arrest response - into its elemental molecular parts has shed light into the mechanisms used by tumors to evade surveillance and cause metastasis.