Sponges [Porifera] are the phylogenetically oldest metazoan phylum still extant today; they share the closest relationship with the hypothetical common metazoan ancestor, the Urmetazoa. During the past 8 years cDNAs coding for proteins involved in cell-cell- and cell-tissue interaction have been cloned from sponges, primarily from Suberites domuncula and Geodia cydonium and their functions have been studied in vivo as well as in vitro. Also, characteristic elements of the extracellular matrix have been identified and cloned. Those data confirmed that all metazoan phyla originate from one ancestor, the Urmetazoa. The existence of cell adhesion molecules allowed the emergence of a colonial organism. However, for the next higher stage in evolution, individuation, two further innovations had to be formed: the immune- and the apoptotic system. Major defense pathways/molecules to prevent adverse effects against microbes/parasites have been identified in sponges. Furthermore, key molecules of the apoptotic pathway(s), e.g., the pro-apoptotic molecule comprising two death domains, the executing enzyme caspases, as well as the anti-apoptotic/cell survival proteins belonging to the Bcl-2 family have been identified and cloned from sponges. Based on these results—primarily obtained through a molecular biological approach—it is concluded that cell-cell- and cell-matrix adhesion systems were required for the transition to a colonial stage of organization, while the development of an immune system as well as of apoptotic processes were prerequisites for reaching the integrated stage. As the latter stage already exists in sponges, it is therefore likely that the hypothetical ancestor, the Urmetazoa, was also an “integrated colony.”