HHS is the federal government's principal agency for protecting the health of all Americans. It administers Medicare, health insurance for people 65 and older and some younger people with disabilities, and works with states to jointly fund Medicaid, health coverage for low-income Americans, together covering more than 150 million people nationwide.

The department also houses the Centers for Disease Control and Prevention (CDC), which tracks and responds to disease outbreaks, the Food and Drug Administration (FDA), which approves new drugs and medical devices and regulates food safety, and the National Institutes of Health (NIH), the world's largest public funder of biomedical research.

HHS is by far the largest federal department by budget, since Medicare and Medicaid alone account for the majority of its roughly $1.7 trillion in annual spending, an amount larger than the entire federal budget of nearly every other country in the world.