The study of death receptor (DR) signaling has led to the discovery of new signaling paradigms, including the first example of direct receptor-mediated activation of a protease (caspase-8) that functions as a second messenger to initiate a 'death cascade' of downstream protease activation. More recently, this receptor system has underscored the importance of ubiquitin modification in NF-kappaB activation. Both degradative lysine 48-linked polyubiquitin and scaffolding lysine 63-linked polyubiquitin have an essential role in signal propagation. Remarkably, a negative feedback process, termed ubiquitin editing, regulates signaling that emanates from certain DRs. Ubiquitin editing is mediated by a complex interplay between the ubiquitination and deubiquitination machinery, resulting in the replacement of signal enhancing lysine 63-linked polyubiquitin with signal extinguishing lysine 48-linked polyubiquitin. The ubiquitination machinery and its regulation in the context of DR signaling are discussed herein.