The cross-talk between heterologous signalling systems of the cell represents a new dimension of complexity in the molecular communication network that governs a great variety of physiological processes. In pathophysiologically transformed cells, key elements of this network could offer unique opportunities for pharmacological intervention. In this article, the current state of knowledge regarding the role of epidermal growth factor (EGF) in such a network is described and the recent advances made in the elucidation of the mechanism underlying EGF receptor transactivation are discussed.