PET/CT with either [11C]choline or [18F]fluorocholine represents a powerful technique for restaging prostate cancer (PCa) patients with biochemical failure. The availability of dedicated PET/CT scanners allows fusioning of morphological and functional images, which enables accurate localization of sites of pathological tracer uptake and ease the differentiation between malignant and benign findings. A noteworthy advantage of this whole-body technique is that it provides information on multiple anatomic sites at a single time. As such, the technique has the capability of distinguishing between local relapse and distant metastases, and therefore has the potential to guide the medical treatment. The positive detection rate of [11C]choline PET/CT varies substantially in relation to the inclusion criteria. Studies which included unselected consecutive patients reported a positive detection rate ranging between 40% and 70%. Serum PSA level represents the single, most important factor affecting the rate of positive scans. Other positive predicitive factors include fast PSA kinetics (PSA velocity, PSA doubling time), advanced pathological state at initial staging, previous biochemical failure, hormone resistance and older age. Recent studies indicate that [11C]choline PET/CT has the potential to early restaging PCa patients for PSA levels lower than 1-1.5 ng/mL. However, more studies are necessary to better define the potential of this technique for low PSA levels. The previously cited risk factors can be used to identify patients that are at greater risk and that might best benefit from PET/CT scans. Patients that develop biochemical failure during androgen deprivation therapy (hormone resistance) have a higher likelihood for a positive [11C]choline PET/CT scan in comparison to patients that are drug naïve (hormone sensitive) and are not required to withdraw the anti-androgenic treatment before PET/CT.