Simple SummaryLymph node involvement is a prognostic determinant in the diagnostic work-up and management of muscle-invasive bladder cancer. Thus, it is crucial to provide an accurate staging of the bladder tumor to better identify the best therapeutic strategies to improve the chances of survival and the quality of life of patients affected by bladder cancer. Positron Emission Tomography/Computed Tomography (PET/CT) has been increasingly used in bladder cancer staging to improve the accuracy of lymph node detection and to overcome the lack of sensitivity and the understaging showed by conventional imaging. The aim of this narrative literature review is to provide an overview of the current evidence on the use of 18F-FDG PET/CT in the diagnosis, staging, and restaging of bladder cancer, with a particular focus on its sensitivity and specificity for the detection of LN metastasis. We aim to provide clinicians with a better understanding of 18F-FDG PET/CT’s potential benefits and limitations in clinical practice. Despite the heterogeneity of the studies in the literature and the lack of a consensus, 18F-FDG PET/CT provides important incremental staging and restaging information that can potentially influence the clinical management of patients affected by muscle-invasive bladder cancer.AbstractIntroduction: Lymph node (LN) involvement is a crucial determinant of prognosis for patients with bladder cancer, and an accurate staging is of utmost importance to better identify timely and appropriate therapeutic strategies. To improve the accuracy of LN detection, as an alternative to traditional methods such as CT or MRI, 18F-FDG PET/CT has been increasingly used. 18F-FDG PET/CT is also used in post-treatment restaging after neoadjuvant chemotherapy. The aim of this narrative literature review is to provide an overview of the current evidence on the use of 18F-FDG PET/CT in the diagnosis, staging, and restaging of bladder cancer, with a particular focus on its sensitivity and specificity for the detection of LN metastasis. We aim to provide clinicians with a better understanding of 18F-FDG PET/CT’s potential benefits and limitations in clinical practice. Materials and Methods: We designed a narrative review starting from a wide search in the PubMed/MEDLINE and Embase databases, selecting full-text English articles that have examined the sensibility and specificity of PET/CT for nodal staging or restaging after neoadjuvant therapy in patients with bladder cancer. The extracted data were analyzed and synthesized using a narrative synthesis approach. The results are presented in a tabular format, with a summary of the main findings of each study. Results: Twenty-three studies met the inclusion criteria: fourteen studies evaluated 18F-FDG PET/CT for nodal staging, six studies examined its accuracy for restaging after neoadjuvant therapy, and three studies evaluated both applications. To date, the use of F-18 FDG PET/TC for detection of LN metastasis in bladder cancer is controversial and uncertain: some studies showed low accuracy rates, but over the years other studies have reported evidence of high sensitivity and specificity. Conclusions: 18F-FDG PET/CT provides important incremental staging and restaging information that can potentially influence clinical management in MIBC patients. Standardization and development of a scoring system are necessary for its wider adoption. Well-designed randomized controlled trials in larger populations are necessary to provide consistent recommendations and consolidate the role of 18F-FDG PET/CT in the management of bladder cancer patients.