Background: Definitive radiotherapy (RT), with or without concurrent chemotherapy, is an alternative to radical cystectomy for patients with localized, muscle-invasive bladder cancer (MIBC) who are either not surgical candidates or prefer organ preservation. There is a paucity of high-quality, prospective data to guide patient selection and management. Objectives: We aim to synthesize a consensus guideline regarding the appropriate use of radiotherapy based upon a systematic review of the available literature. Methods: We performed a Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) literature review using the PubMed and Europe PMC databases. Articles published before and up to 3/18/2019 were included in the systematic review. Search parameters were prospectively recorded and sequentially refined for relevance of article titles. Studies were included for full manuscript review after screening of the abstracts. Based upon findings of the literature review, critical management topics were identified and reformulated into consensus questions. An expert panel was assembled to address key areas of both consensus and controversy. Results: A total of 761 articles were screened, of which 60 were published between 1975 to 2019 and included for full review. Of these, there were seven well-designed studies, 20 good quality studies, 27 quality studies with design limitations, and six references not suited as primary evidence. While early studies included node-positive MIBC, contemporary trials mostly exclude this population from definitive radiotherapy treatments. Adjuvant radiotherapy after cystectomy was not included due to lack of high-quality data or clinical utilization. An expert panel consisting of 14 radiation oncologists, one medical oncologist, and one urologist from 14 institutions was assembled. We identified four clinical variants of MIBC: surgically fit patients who wish to pursue organ preservation; patients surgically unfit for cystectomy; patients medically unfit for cisplatin-based chemotherapy; and borderline cystectomy candidates based on age with unilateral hydronephrosis and normal renal function. After synthesis of the evidence, we identified key areas of controversy, including use of definitive radiotherapy for patients with negative prognostic factors (e.g. hydronephrosis, multi-focal disease, extensive CIS), appropriate radiotherapy dose, fractionation, fields and technique when used, and chemotherapy sequencing and choice of agent. Conclusions: A systematic review of the literature was performed to assess the evidence for radiotherapy for patients with localized MIBC. Overall, there is a paucity of level-one evidence to guide clinical practice. Studies vary significantly with regards to patient selection, chemotherapy utilization, and radiotherapy technique. A consensus guideline on the appropriateness of RT for MIBC may aid practicing oncologists in bridging the gap between data and clinical practice.