With the cable approximation, Wielfrid Rall opened the way to realistic multi-compartment electrical models . This approach assimilates a portion of dendrite to a simple electrical circuit that can then be assembled serially. These models quickly spanned several scales, encompassing synaptic contacts between neurons , models of multicellular structures , and even of several coupled brain structures . The availability of powerful and easy to use simulators to develop such multi-compartment models, like NEURON  and GENESIS  allowed the construction of extremely detailed models of neurons. Those models include not only electrical behaviour, but also ion diffusion . Advanced computing facilities now permit the development of large heterogeneous neuronal assemblies, where each neuron possess a realistic geometry and specific electrophysiological properties determined by a given set of ion channels. The most ambitious project in this domain may be the Blue Brain Project , which aims to simulate a whole mammalian cerebral cortex using a super-computer. As a proof-of-concept, simulations of a neocortical column containing 10,000 neurons have been run. In parallel to the development of electrical models, neurobiologists started to model neuronal signalling using the concepts of chemical kinetics, already widely used in biochemistry . The coupling of reaction kinetics with single particle diffusion and realistic spatial representation now allows the simulation of neuronal signalling at a level of detail only dreamt of before . At the end of last century, two decades of molecular and cellular neurobiology had demonstrated that to reach a comprehensive understanding of neuronal signalling, we ought to consider both electrical and biochemical signal transduction [18,19].