Eleftherios Mylonakis serves as the chair of medicine at Houston Methodist Hospital, Charles and Anne Duncan Presidential Distinguished Chair, and professor of medicine at Weill Cornell Medical College and the Houston Methodist Academic Institute. Previously, he held the position of Charles C.J. Carpenter Professor of Infectious Disease at Brown University for a decade. During that time, Mylonakis also served as chief of infectious diseases, director of the Centers of Biomedical Research Excellence Center for Antimicrobial Resistance and Therapeutic Discovery, professor of molecular microbiology and immunology, and contributed to the Alpert Medical School of Brown University as assistant dean for outpatient investigations and director of the Center for Outpatient and Longitudinal Medical Research. Prior to his work at Brown, Mylonakis was an attending physician at Massachusetts General Hospital and associate professor at Harvard Medical School.

Mylonakis' research focus encompasses both clinical and laboratory studies, investigating host and microbial factors of infection, as well as the discovery of antimicrobial agents. He utilizes diverse tools and interdisciplinary approaches, such as molecular biology, immunology, biostatistics, decision-making analysis, risk assessment, outcomes research, and cost-effectiveness studies. His work often involves using mammalian and invertebrate model host systems to identify novel antimicrobial compounds and uncover evolutionarily conserved aspects of microbial virulence and the host response.

The Mylonakis laboratory's studies on host-pathogen interactions and antimicrobial drug discovery involve the use of biostatistics, whole-animal high-throughput screening, and imaging-based screening to identify lead compounds and explore molecular mechanisms employed by pathogens against various metazoan hosts. These investigations have revealed novel virulence factors, cross-kingdom pathogen interactions, and evolutionarily conserved traits related to host virulence and immune responses during infections. More recently, the focus has expanded to the investigation of antimicrobial compounds, leading to a substantial screening effort of over 90,000 compounds and the identification of numerous scaffolds.

Mylonakis' significant contributions include nearly 500 articles published and cited over 30,000 times, eight patents, and co-editorship of seven books on infectious diseases, covering topics like emerging strategies in antimicrobial drug discovery, principles and practices of antimicrobial stewardship, and recent advancements in model hosts.