Metastasis is usually responsible for mortality in patients suffering from muscle invasive bladder cancer. Whilst expression of a great number of genes and their protein products have been associated with metastasis and/or poor prognosis in bladder cancer, evidence that they actively drive the metastatic process, and hence make potentially good therapeutic targets, is often lacking. This is due to the limited number and application of effective animal models which reflect the pathogenesis of the human disease. In this review I will discuss the processes involved in metastasis, consider the established animal models of bladder cancer progression and metastasis, and review the evidence for a role of various gene products in this process. Consideration of clinical studies in conjunction with evidence from experimental animal models reveals that the tyrosine kinase receptor erbB1/EGFR, the calcium binding protein S100A4 and the the cell cycle arrest/apoptosis-inducing p53 protein are amongst the most promising targets for therapy against metastatic disease in patients with bladder cancer.