Over the last decade, accumulating data have demonstrated the presence of 'classical' signalling molecules on endomembranes, including endosomes and the Golgi complex. It is now clear that through these signalling molecules, endomembranes can serve two functions: one is to elaborate and relay signalling initiated at the plasma membrane, and the other is to initiate new signalling in response to stimuli originating from the endomembranes themselves. Here, we have examined this emerging paradigm, with particular emphasis on a novel Golgi-based signalling cascade. This system senses, and is activated by, endoplasmic reticulum chaperones that arrive at the Golgi complex during constitutive secretion; these bind to the KDEL receptor and activate the Src family kinases. These, in turn, positively regulate the intra-Golgi transport machinery. This system thus coordinates the initiating process, the membrane input, with an increased membrane output. In more general terms, it responds with signals to an endogenous event. In this respect, it is similar to the unfolded protein response, a complex cell reaction to the accumulation of unfolded proteins in the endoplasmic reticulum, that is, to our knowledge the only other examples of inter-organelle signalling initiated within the cell. However, in contrast to the Golgi-based signalling pathway, this unfolded protein signalling is generally activated by pathological conditions. We propose that inter-organelle signalling is a mechanism by which different compartments of eukaryotic cells coordinate their functions.