Mesothelia in the adult vertebrate are the simple squamous epithelia covering all coelomic organs and body cavities. Until recently, analysis of the generation and differentiative potential of mesothelia in organogenesis has largely focused on development of visceral mesothelium of the heart; the epicardium and its progenitor, the proepicardium. Here, we review emerging data on the development and differentiation of serosal mesothelium, the covering of the gastrointestinal tract. This literature demonstrates that serosal mesothelium is generated through a completely different mechanism than that seen in the heart suggesting that commitment of progenitors to this cell lineage does not follow a common pathway. The differentiative potential of serosal mesothelium is also discussed in comparison to that observed for progeny of the proepicardium/epicardium. In our review of the literature, we point out gaps in our understanding of serosal mesothelial development and that of mesothelial development as a whole.