Components of the ESCRT (endosomal sorting complex required for transport) machinery mediate endosomal sorting of ubiquitinated membrane proteins. They are key regulators of biological processes important for cell growth and survival, such as growth-factor-mediated signalling and cytokinesis. In addition, enveloped viruses, such as HIV-1, hijack and utilize the ESCRTs for budding during virus release and infection. Obviously, the ESCRT-facilitated pathways require tight regulation, which is partly mediated by a group of interacting proteins, for which our knowledge is growing. In this review we discuss the different ESCRT-modulating proteins and how they influence ESCRT-dependent processes, for example, by acting as positive or negative regulators or by providing temporal and spatial control. A number of the interactors influence the classical ESCRT-mediated process of endosomal cargo sorting, for example, by modulating the interaction between ubiquitinated cargo and the ESCRTs. Certain accessory proteins have been implicated in regulating the activity or steady-state expression levels of the ESCRT components, whereas other interactors control the cellular localization of the ESCRTs, for example, by inducing shuttling between cytosol and nucleus or endosomes. In conclusion, the discovery of novel interactors has and will extend our knowledge of the biological roles of ESCRTs.