As prostate cancer is not a single disease, it is important to identify the pivotal pathway in the patient being treated. The molecular environment is the site of current oncological research to define new therapeutic targets for hormone-refractory disease, offering the potential to eventually individualize treatment through stratification of pathways. Targets may be validated either phenotypically (e.g. androgen receptor, cadherin) or functionally (e.g. prostate cancer-specific genes). In addition, several other candidates are potentially suitable, while others await discovery. Important initial steps have been made in the search for prostate cancer stem cells; identifying stem cells and the stromal, hormonal, and other signalling molecules that influence their behaviour would have important implications for managing prostate cancer. Although individual therapeutic pathways might be ineffective in a particular molecular environment, combinations of approaches might be capable of producing synergistic effects. A multimodal approach thus might be the best solution. Determining where best to search for a molecular target, and validating whether the target is associated with a sufficiently aggressive malignant process to justify further study is difficult, but the potential benefits are enormous.