From 1975 to 1999, Osterholm served in various roles at the Minnesota Department of Health (MDH), including as state epidemiologist and Chief of the Acute Disease Epidemiology Section from 1984 to 1999.

[7] In 2005, HHS Secretary Mike Leavitt appointed Osterholm to the National Science Advisory Board on Biosecurity.

[11] He is a past president of the Council of State and Territorial Epidemiologists and served on the CDC's National Center for Infectious Diseases Board of Scientific Counselors from 1992 to 1997.

He is a frequent consultant to the World Health Organization, the NIH, the Food and Drug Administration, the Department of Defense, and the CDC.

[7][14] In March 2017, Osterholm and Mark Olshaker published the critically acclaimed Deadliest Enemy: Our War Against Killer Germs.

[15][16][17] Richard Preston, author of The Hot Zone, wrote that the book "looks at the threat of emerging diseases with clarity and realism, and offers us not just fear but plans.

Osterholm has also published multiple commentaries in The New York Times, most recently on the repercussions of reductions in funding for research and vaccine development, and how this affects our ability to respond to new infectious disease threats.

[7] Osterholm has received honorary doctorates from Luther College[22] and Des Moines University,[23] and is a member of the Institute of Medicine of the National Academy of Sciences.