To say that thrombin is a multi-functional protein is rather to understate the case. It is the key enzyme involved in haemostasis, playing important roles at all levels of complexity. First, in the coagulation cascade, thrombin converts fibrinogen into fibrin, which is readily cross-linked to form a clot (reviewed in [1, 2]); secondly, thrombin activates blood platelets, causing aggregation and secretion [3, 4]; and thirdly, thrombin can elicit mitogenic responses from vascular smooth-muscle cells [5, 6]. This latter property is probably most significant in the renewal of damaged blood-vessel walls. Additionally, thrombin is able to elicit responses from cell types as diverse as macrophages [7], monocytes [8] and neutrophils [9]. Perhaps more surprisingly, it is able to regulate neurite outgrowth from cells of neuronal origin [10] and initiate resorption of bone cells [11]. All of these properties of thrombin appear to rely on its action as a serine proteinase, since modification (either chemically [12–14] or mutationally [15–17]) which destroys its proteolytic activity leads to a loss of biological activity. These crucial findings have been explained to a large extent by the recent elegant characterization of a novel, widely expressed thrombin receptor which is activated by proteolytic cleavage rather than by ligand (protein) binding [18, 19]. At the same time as elucidation of the mechanism of thrombin signalling there has been a dramatic increase in our understanding of how thrombin signals are mediated within the cell. This therefore seems an appropriate time to assess our current knowledge and perhaps to try to predict areas where the greatest advances will be made in the immediate future. In this review, because of limitations in length, emphasis will be placed on recent advances, in particular on the characterization of the thrombin receptor and in the mechanisms of intracellular signalling. Whilst most studies of thrombin have concentrated on its action on cells involved in blood clotting and wound healing, it is now becoming apparent that it can modulate the growth and differentiation status of cells of neuronal origin. A consideration of recent advances in this area of study will form the third major theme of this review.