Locally advanced esophageal cancer has a poor prognosis, while an increasing number of patients are diagnosed with that. Neoadjuvant therapy has become a hot topic in treating locally advanced esophageal cancer to improve its survival benefit. The efficacy of neoadjuvant therapy followed by surgery has been confirmed by many studies, and neoadjuvant chemoradiotherapy and neoadjuvant chemotherapy are included in the guidelines. In recent years, targeted therapy and immunotherapy have emerged, and more studies are evaluating the efficacy of combining them with neoadjuvant therapy for operable esophageal cancer patients. Even though the preliminary data is disappointing, many trials are still under investigation without improving survival benefits. New indexes used as surrogate endpoints (e.g., major pathologic response and pathological complete response) are emerging to accelerate the development and approval of neoadjuvant drugs. This review summarized the research progress in neoadjuvant therapy for locally advanced esophageal cancer and discussed which primary endpoint should be used in neoadjuvant therapy trials.© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.