In the majority of cases, death from bladder cancer results from metastatic disease. Understanding the closely linked mechanisms of invasion, metastasis and angiogenesis in bladder cancer has allowed us to develop new therapeutic strategies that harbor the promise of decisive improvements in patient survival. The essential link between cell based experiments and the translation of novel agents into human patients with bladder cancer is the animal model. With emphasis on the orthotopic xenograft model, this review outlines some key mechanisms relevant to angiogenesis and the development of metastasis in bladder cancer. We highlight especially pathways related to MMP-9, IL-8, VEGF and EGFR. Most commonly, expression patterns of these markers in patients have correlated to disease progression and patient survival, which has led to laboratory investigations of these markers and eventually novel targeted therapies that are translated back into the clinic by means of clinical trials. Although imperfect in their translatability into clinical efficacy, animal models remain a critical tool in bladder cancer research.