Different strategies have been used in an attempt to understand the neurobiology of opioid addiction. Here, Michéle Simonato initially discusses the identification of key anatomical areas involved in the phenomenon and purposes an explanation of opioid addiction based on the theory of complexity. The variable importance of direct and indirect effects in phenotypically different neuronal populations can imply differences in the adaptive changes that occur with chronic morphine exposure. Opioid addiction is therefore proposed as a complex multicellular event, where individual neurones differentially adapt both on the basis of the signals they receive and of their second messengers and genetic programmes.