Dr. Elihu H. Estey (July 15, 1946–October 8, 2021), an international leader in leukemia research, is mourned by the Leukemia Department at MD Anderson Cancer Center. On the morning of Saturday September 9, 2021, one by one, members of the Department of Leukemia at MD Anderson learned, via phone call or text message, about the sudden, tragic, and unexpected death of Dr. Elihu H. Estey. Apparently, Dr. Estey, Eli for us, was analyzing data and writing a paper, the thing that he enjoyed the most, at home when this happened. The unexpected passing of Dr. Estey constitutes a major loss to the field of leukemia research and care. Dr. Estey was born in New York in 1946. After attending college at Yale University, where he obtained a degree in mathematics in 1968, and obtaining a medical degree from Johns Hopkins University in 1972, he went to receive further training in neurology at New York University. In 1978, he joined MD Anderson as a clinical fellow and after a short hiatus serving at the National Cancer Institute; he joined MD Anderson again in 1984 as a faculty member where he was eventually named full professor in 1993 and chief of the section of myelodysplatic syndrome (MDS) and acute myelogenous leukemia (AML) in 1997. In Houston, Dr. Estey became a member of a group of individuals that in time would transform the care of patients with leukemia and the approach to leukemia research. These include the late Dr. Emil Freireich, Dr. Michael Keating leader of chronic lymphocytic research at MD Anderson, after major discoveries in AML, and Hagop Kantarjian who focused on chronic myelogenous leukemia and acute lymphocytic leukemia and now leads the Department of Leukemia at MD Anderson. Dr. Estey focused on the study of myelodysplastic syndrome and AML. These four individuals constituted the original nucleus of what is now the largest leukemia research program in the world with over 30 active faculty members, 2000 new patients evaluated yearly and over 100 active clinical trials. This is in part thanks the efforts and mentorship of Dr. Estey. Dr. Estey published over 700 papers as reported in PubMed. Together with Drs. Plunkett and Keating, his early work focused on the study of cytarabine dosing and schedules in the treatment of AML and combinations with nucleoside analogs that eventually resulted in combinations such as FLAG-Ida, FA, FIA, CLIA that are now standard of care at MD Anderson and are fundamental in the treatment of core binding factor AML. Early on, he also developed an interest on the study of outcomes in AML that allowed us to understand the natural history of this disease in the context of therapy. In parallel, he led critical studies in the treatment of acute promyelocytic leukemia that two decades later, and thanks to his collaboration with the Spanish and Italian groups, resulted in highly curative nonchemotherapy-based approaches for patients with APL. At MD Anderson, he was recognized by his deep knowledge, and incorporation, of new statistical methods for clinical trial design. This started in the 1990s after his long-term collaboration with Dr. Peter Thall that resulted in the use of Bayesian methods to study disease outcomes that resulted for instance in the development of adoptive randomization designs to accelerate the speed of clinical trials conduction. In 2008, after retiring from MD Anderson, Dr. Estey moved to the University of Washington and Fred Hutchinson Cancer Center in Seattle where he continued to work and mentor the distinguished faculty at that center and continue to contribute to the treatment of leukemia. At the personal level, Dr. Estey was a very unique individual. He was an extraordinarily generous mentor and colleague. Personally, he helped me (GG-M) understand MDS, trial design, and approach to research in general that had a significant impact on my career development. He also mentored Dr. Farhad Ravandi in the field of AML and APL. You could see Dr. Estey at his desk analyzing data using computer language so archaic that only he and his beloved Sherry Pierce RN understood. Mrs. Pierce, a key member of our department, has maintained and used the leukemia patient database for several decades and was Dr. Estey long-term research partner, a collaboration that resulted in thousands of manuscripts and probably contributed the most to leukemia clinical care around the world. In the clinic, he used the same approach. When evaluating a new patient 59 years of age in CR2 and with a WBC of 2.0, you could see him typing in the clinic computer keyboard trying to get an answer from that database about what the expected outcome could be under different scenarios. I wonder what a newly born Eli Estey would be like today with new whole genome sequence techniques and access to large-scale artificial intelligence platforms. He always had a constructive but critical view of data. Every time we shared a paper with him, we knew that he was going to take his time to review it and give you an alternative answer. At the end, and with a little bit more work, and different analysis, you came with a better answer and paper or grant. He was a great collaborator outside MD Anderson walls and his interactions with members of the European leukemia community were very fruitful in particular with the late Drs. Francesco Lo Coco and Miguel Sanz helping him amplify his ideas on the treatment of APL. He had a very curious mind and his questions sometimes were simple but had deep implications. For instance, a trial designed to study the impact of neutropenic diets in patients with leukemia probed that our standard practice (“clean diet”) was not only not beneficial but potentially detrimental or when he produced an analysis of how many of the American Society of Hematology (ASH) presentations were ever published in a peer-reviewed journal. Obviously questioning the role of the meeting. He later presented at ASH this data as a poster in green hand-written pieces of paper. When asked about why not doing a formal poster, the answer was why to waste resources. Indeed, I do not think he had a printer in his office. He liked to exhibit some well-mannered eccentric behaviors such as writing his notes in green or signing under a pseudonym (I guess we could not do this in EPIC today) and did not care about the administrative structure of the center, always focusing on his data. That was very refreshing. When in 2008, he announced that he was leaving MD Anderson, I felt that we were losing a key member of our department, someone that always brought an alternative view to our conclusions and helped us better understand our own results. Over the years, we continued to interact and collaborate. The Covid-19 pandemic put a hold to our in-person meetings at ASH or other venues and to a few minutes of chit chat about politics, leukemia, or MDS or maybe baseball. Dr. Elihu Estey is going to be deeply missed by our community and the MD Anderson family in particular. We send our biggest condolences to his wife and his children. The authors declare no conflict of interest.