Skeletal metastases are very common in prostate cancer and represent the main metastatic site in about 80% of prostate cancer patients, with a significant impact in patients' prognosis. Early detection of bone metastases is critical in the management of patients with recently diagnosed high-risk prostate cancer: radical treatment is recommended in case of localized disease; systemic therapy should be preferred in patients with distant secondary disease. Bone scintigraphy using radiolabeled bisphosphonates is of great importance in the management of these patients; however, its main drawback is its low overall accuracy, due to the nonspecific uptake in sites of increased bone turnover. Positron-emitting radiopharmaceuticals, such as fluorine-18-fluorodeoxyglucose, choline-derived drugs (fluorine-18-fluorocholine and carbon-11-choline) and sodium fluorine-18-fluoride, are increasingly used in clinical practice to detect metastatic spread, and particularly bone involvement, in patients with prostate cancer, to reinforce or substitute information provided by bone scan. Each radiopharmaceutical has a specific mechanism of uptake; therefore, diagnostic performances may differ from one radiopharmaceutical to another on the same lesions, as demonstrated in the literature, with variable sensitivity, specificity, and overall accuracy values in the same patients. Whether bone scintigraphy can be substituted by these new methods is a matter of debate. However, greater radiobiological burden, higher costs, and the necessity of an in-site cyclotron limit the use of these positron emission tomography methods as first-line investigations in patients with prostate cancer: bone scintigraphy remains the mainstay for the detection of bone metastases in current clinical practice.