The proteins termed TLE in humans, Grg in mice and Groucho in Drosophila constitute a family of transcriptional corepressors. In mammalians there are five different genes encoding an even larger number of proteins. Interactions between these TLE/Grg proteins and an array of transcription factors has been described. But is there any specificity? This review tries to make a case for a non-redundant function of individual TLE/Grg proteins. The specificity may be brought about by a tightly controlled temporo-spatial expression pattern, post-translational modifications, and subtle structural differences leading to distinct preferences for interacting transcription factors. A confirmation of this concept will ultimately need to come from genetic experiments. © 2005 Wiley-Liss, Inc.