In 2009, five monophyletic Escherichia clades were described and referred to as "cryptic" based on the inability to distinguish them from representative E. coli isolates using diagnostic biochemical reactions. Since this original publication, a number of studies have explored the genomic, transcriptomic, and phenotypic diversity of cryptic clade isolates to better understand their phylogenetic, physiological, and ecological distinctiveness with respect to previously named Escherichia species. This chapter reviews the original discovery of the cryptic clades, discusses available evidence that some are environmentally adapted, and evaluates current support for taxonomic designations of these microorganisms. The importance of these clades to clinical research, epidemiology, population genetics, and microbial speciation is also discussed.