In 2001, Ramachandran and Hubbard introduced the cross-activation model of grapheme-colour synaesthesia. On the occasion of its 10-year anniversary, we review the evidence from experiments that have been conducted to test the model to assess how it has fared. We examine data from behavioural, functional magnetic resonance imaging (fMRI), anatomical studies (diffusion tensor imaging and voxel-based morphometry), and electroencephalography (EEG) and magnetoencephalography (MEG) studies of grapheme-colour synaesthesia. Although much of this evidence has supported the basic cross-activation hypothesis, our growing knowledge of the neural basis of synaesthesia, grapheme, and colour processing has necessitated two specific updates and modifications to the basic model: (1) our original model assumed that binding and parietal cortex functions were normal in synaesthesia; we now recognize that parietal cortex plays a key role in synaesthetic binding, as part of a two-stage model. (2) Based on MEG data we have recently collected demonstrating that synaesthetic responses begin within 140 ms of stimulus presentation, and an updated understanding of the neural mechanisms of reading as hierarchical feature extraction, we present a revised and updated version of the cross-activation model, the cascaded cross-tuning model. We then summarize data demonstrating that the cross-activation model may be extended to account for other forms of synaesthesia and discuss open questions about how learning, development, and cortical plasticity interact with genetic factors to lead to the full range of synaesthetic experiences. Finally, we outline a number of future directions needed to further test the cross-activation theory and to compare it with alternative theories.