This review explores possible mechanisms by which the neurofibromatosis type-2 tumour suppressor Merlin regulates contact-dependent inhibition of proliferation. Starting from an evolutionary perspective, the concurrent emergence of intercellular contacts and proliferation control in multicellular organisms is first considered. Following a brief survey of the molecular and subcellular milieus in which merlin performs its function, the importance of different cellular and biological contexts in defining the function of merlin is discussed. Finally, an integrated model for merlin and the Ezrin, Radixin, and Moesin (ERM) proteins functioning in the regulation of cellular interfaces is proposed.