There is strong evidence for a genetic component in schizophrenia but its precise nature remains unclear. Positional cloning and studies of potential candidate genes offer prospects for progress. The diagnosis of schizophrenia can now be made reliably but questions remain over the most valid phenotypic definition. To deal with this and uncertainties regarding mode of transmission a 'polydiagnostic' approach is advisable. A wealth of new DNA markers has enhanced the potential for linkage studies which have so far focused on large multiply-affected families. Multi-centre collaborative studies that are currently under way are likely to identify genes of major effect but other strategies are required if it turns out that most cases result from the combined effect of multiple genes.