He was in the first entering class of the Mount Sinai School of Medicine in 1968, and graduated in 1972 with the Elster Prize for highest academic standing.

He moved to Boston in 1978, becoming an assistant professor of medicine at Harvard Medical School, and chief of the Diabetes Unit at Harvard-affiliated Beth Israel Hospital.

[16] This discovery elucidated a rare cause of diabetes,[17] advanced the field of membrane receptor biology and provided an important tool for research on insulin action.

[26] With Maratos-Flier, he studied the participation of neuropeptide MCH in feeding behavior and energy balance;[27] and the role of FGF21 in metabolic regulation.

[29] In 2005, he reported the possible role of adult hypothalamic neurogenesis in the control of energy balance;[30] Regarding inflammatory phenomena in metabolic disease, Flier helped establish that Toll-like receptor 4 (TLR4) activation in adipocytes and macrophages mediates inflammation accompanying obesity, and subsequent insulin resistance in diabetes.

[32] Since stepping down as dean, Flier has increasingly contributed policy-oriented publications focusing on a number of issues affecting health care and biomedical research in current times, among them: health care reform[33] and its sustainability,[34] enhancing US health provider workforce,[35] the pros and cons of prevailing credit attribution practices in academia and industry,[36] the realities and options linked to the irreproducibility of research results,[37] improving the institutional handling of scientific misconduct,[38] the obsolescence of distinctions between basic and translational biomedical research,[39] and the complexities behind conflict of interest (COI) disclosure.

She is an endocrinologist and Professor of Medicine at Harvard Medical School,[44] and currently a director of clinical research at Alynylam Pharmaceuticals.