Abstract Purpose During the last decade, [18F]F-choline positron emission tomography (PET) had a rising role in prostate cancer (PCa) imaging. However, despite auspicious premises, [18F]F-choline PET is not currently recommended for the evaluation of response to therapy assessment in PCa, mainly due to the lack of large-scale prospective trials. Methods We report the cases of seven patients affected by PCa, in which [18F]F-choline PET (either with computed tomography—CT or magnetic resonance imaging—MR) contributed significantly in the systemic therapy response evaluation. Results and conclusion [18F]F-choline PET/CT or PET/MR demonstrated to be a useful imaging modality in the assessment of response to systemic therapy in metastatic PCa patients, irrespective of the stage of disease (either in hormone sensitive and in castrate resistant condition) and the kind of systemic treatment. In most cases, PSA serum values and [18F]F-choline PET showed a synchronous disease evolution after systemic therapy. ADT can alter [18F]F-choline uptake, therefore the time of scan should be correctly planned. Finally, PET/CT with [18F]F-choline is a useful tool for reinforcing the identification of metastatic disease in case of a switch from metastatic castration sensitive to castration resistant PCa.