Id helix-loop-helix (Id HLH) proteins are negative regulators of basic HLH transcription factors. They are expressed during embryonic development and are important for the regulation of cell phenotypes in adults. They participate in the molecular networks controlling cell growth, differentiation, and carcinogenesis, through specific basic HLH and non-basic HLH protein interactions. Recent in vitro and in vivo data implicate Id HLH as important orchestrating proteins of homeostasis in glandular and protective epithelia. In particular, Id proteins have been reported to be involved in cell behavior in epidermis, respiratory system, digestive tract, pancreas, liver, thyroid, urinary system, prostate, testis, endometrium, cervix, ovary, and mammary gland. The purpose of this review is to summarize the evidence implicating Id proteins in the regulation of mammalian epithelial cell phenotypes.