The serine protease autotransporters of the Enterobacteriaceae (SPATEs) represent a group of large-sized, multi-domain exoproteins found only in pathogenic enteric bacteria. These proteins contain a highly conserved channel-forming C-terminal domain, which functions together with YaeT/Omp85 to facilitate secretion of the passenger domain to the cell surface. The C-terminal domain also mediates autoproteolytic cleavage, which releases the passenger from the bacterial cell. The passenger folds into a characteristic parallel beta-helical stalk-like structure with an N-terminal globular domain that performs serine proteolytic activity. Here, we review and discuss recent findings that have led to a better understanding of these unique features in this virulence protein family, including their biogenesis, structural architecture, sequence variation, sub-grouping, evolution and biochemical function.