Current treatment of locally advanced esophageal cancers (ECs) centres on a multimodal approach regardless of histology. While surgery remains the mainstay of curative intent therapy, its implementation alone results in suboptimal outcomes, which have improved significantly with the increased utilization of induction regimens comprising of concurrent chemoradiation (CRT) or chemotherapy alone followed by surgery. Due in large part to the positive results of the CROSS trial, neoadjuvant CRT has become the predominant standard applied in the West. However, the bulk of the data published to date suggests that a more nuanced approach to the management of locally advanced EC is required with respect to the application of radiation, which related to the differential sensitivity of esophageal adenocarcinoma (EAC) and esophageal squamous cell carcinoma (SCC) to radiation. While the latter demonstrates excellent radiosensitivity, which has translated into improved survival outcomes, the same cannot be said for patients with EAC who may be subject to greater toxicity without any benefit. Herein, the differential effectiveness of CRT in patients with EAC versus SCC is highlighted, with a focus on the randomized evidence to date.