Numerous attempts towards improving patient management by molecular staging have been fruitless so far. No single molecular parameter is routinely analyzed in prostate cancer tissue. This may be partly due to genuine properties of prostate cancer that may make this tumor a difficult target. Furthermore, inherent logistical problems result in a shortage of prostate cancer tissue for research purposes. For the future, it can be hoped that the availability of more powerful molecular techniques in combination with better tissue archives will allow more rapid progress. Powerful DNA array and proteomics methods allow the systematic analysis of virtually all genes of a cancer on the DNA, RNA, and protein level. Although such approaches are sometimes labeled as “fishing expeditions,” it cannot be totally disregarded that the simultaneous analysis of all genes has a high likelihood of identifying significant new information. In future, one of the major scientific challenges will be the validation of several potential biomarkers in large enough and clinically well-characterized patient cohorts. In particular, studies on needle core biopsies and hormone refractory cancers are imperatively needed for investigating the natural history of the disease or to discover potential predictive markers for radiation therapy and new therapeutic target genes to answer the clinically most important questions for optimal clinical decision making in prostate cancer patients: which patients will not require local therapy? If local therapy is needed, what is the treatment of choice? What medications should be given if metastases are present?