In recent years, stochastic modelling has emerged as a physically more realistic alternative for modelling in vivo reactions. There are numerous stochastic approaches available in the literature; most of these assume that observed random fluctuations are a consequence of the small number of reacting molecules. We review some important developments of the stochastic approach and consider its suitability for modelling intracellular reactions. We then describe recent efforts to include the fluctuation effects caused by the structural organisation of the cytoplasm and the limited diffusion of molecules due to macromolecular crowding. (C) 2004 Elsevier Ltd. All rights reserved.