Growth factors and their receptors are significant to the biology of transitional cell carcinoma of the bladder. In this context, characterization of gene expression, amplification, and mutation has established the relevance of receptors as potential targets of novel therapeutic agents. Because these characteristics vary across disease states, they may serve as prognostic indicators of recurrence, progression, response to therapy, and mortality. This review focuses on the prognostic value of the human epidermal growth factor receptor family, including epidermal growth factor receptor (EGFR), human EGFR-2 (HER2), HER3, HER4, vascular endothelial growth factor receptor (VEGFR), and fibroblast growth factor receptor-3 (FGFR3). EGFR and HER2 seem to indicate a poor prognosis, and HER4 and FGFR3 appear to be favorable prognostic indicators. However, validation studies are required to answer many remaining questions.