Several well-validated susceptibility genes for schizophrenia have now been identified. We suggest that these genes can be divided into two broad classes. Those in the first class have direct effects on synaptic plasticity mediated through actions at glutamatergic synapses; those in the second class impact on meso-limbic dopamine signalling. We argue that these genes have an interactive effect on risk for psychosis and that this interaction can be understood in the context of associative learning theory. We illustrate how genetic variation in genes from these classes can contribute to the development of psychosis using data from the Edinburgh High Risk Study of schizophrenia.