Introduction Peri-hilar cholangiocarcinoma is an aggressive bile duct cancer. Long term survival is possible with margin-negative surgery. Historically, unresectable disease was approached with non-curative treatment options. In recent decades, an innovative approach of neoadjuvant chemoradiation and liver transplantation has demonstrated long term survival for highly select patients. Areas Covered This is a critical analysis of studies published to date on neoadjuvant chemoradiation and liver transplantation for select patients with peri-hilar cholangiocarcinoma. A PubMed literature search was conducted for years 1970-2020 with the following search criteria: ["hilar" OR "peri-hilar" AND "cholangiocarcinoma"] AND ["treatment" OR "transplantation" OR "survival" OR "outcome"]; "neoadjuvant chemoradiation" AND "unresectable cholangiocarcinoma". All peer-reviewed original research studies were selected for review. Expert Opinion Neoadjuvant chemoradiation and liver transplantation for patients with early stage unresectable peri-hilar cholangiocarcinoma can achieve long term survival in the highly select patients who survive to transplantation without disease progression. There are observed differences in survival for patients with PSC-associated versus de novo cholangiocarcinoma and transplanted versus resected patients; however, these differences are not contextualized by established tumor and patient factors that influence recurrence and survival. Therefore, these results must be interpreted within the limitations of the study designs upon which they are based.