•IDRs exist as diverse and dynamic populations of interchanging structural conformations.•Subsets of these conformations can have distinct functions.•Cell state changes can shift the structural properties of IDRs to modulate their function.•The link between the (un)structure and function of IDRs is poorly understood. After two decades of research, intrinsically disordered regions (IDRs) are established as a widespread phenomenon. The growing understanding of the significant functional role of IDRs has challenged the structure–function paradigm, proving irrefutably that a stably folded structure is not a strict requirement for function. Nonetheless, (un)structure–function relationships remain at the core of IDR-mediated interactions. An IDR can populate a continuously transitioning continuum of structural conformations from fully disordered to stable globular states. In these ensembles, only subsets of conformations are binding competent, with intramolecular IDR contacts serving as important intermolecular binding determinants. Here, we review our current understanding of different types of intramolecular IDR interactions, their effects on IDR complex formation and their modes of biological regulation.