Most malignancies have increased glycolysis for energy requirement of rapid cell proliferation, which is the basis for tumor imaging through glucose analog FDG (2-deoxy-2-fluoro-D-glucose) with positron emission tomography. One of significant characteristics of prostate cancer is slow glycolysis and low FDG avidity. Recent studies showed that prostate cancer is associated with changes of fatty acid metabolism. Several enzymes involved in the metabolism of fatty acids have been determined to be altered in prostate cancer relative to normal prostate, which is indicative of an enhanced beta-oxidation pathway in prostate cancer. Increased fatty acid utilization in prostate cancer provides both ATP and acetyl-coenzyme A (CoA); subsequently, increased availability of acetyl-CoA makes acceleration of citrate oxidation possible, which is an important energy source as well. Dominant fatty acid metabolism rather than glycolysis has the potential to be the basis for imaging diagnosis and targeted treatment of prostate cancer.