The kinase-inducible domain interacting (KIX) domain is a highly conserved independently folding three-helix bundle that serves as a docking site for transcription factors, whereupon promoter activation and target specificity are achieved during gene regulation. This docking event is a harbinger of an intricate multi-protein assembly at the transcriptional apparatus and is regulated in a highly precise manner in view of the critical role it plays in multiple cellular processes. KIX domains have been characterized in transcriptional coactivators such as p300/CREB-binding protein and mediator of RNA polymerase II transcription subunit 15, and even recQ protein-like 5 helicases in various organisms. Their targets are often intrinsically disordered regions within the transactivation domains of transcription factors that attain stable secondary structure only upon complexation with KIX. In this article, we review the KIX domain in terms of its sequence and structure and present the various implications of its ability to act as a transcriptional switch, the mechanistic basis of molecular recognition by KIX, its binding specificity, target promiscuity, combinatorial potential and unique mode of regulation via allostery. We also discuss the possible roles of KIX domains in plants and hope that this review will accelerate scientific interest in KIX and pave the way for novel avenues of research on this critical domain.