He shared the 1994 Nobel Prize in Physiology or Medicine with Alfred G. Gilman for "their discovery of G-proteins and the role of these proteins in signal transduction in cells."

[3] After graduating from the Baltimore City College high school, he entered Johns Hopkins University in 1943, with interests in biology and French existential literature.

In 1985, Rodbell became Scientific Director of the NIH's National Institute of Environmental Health Sciences in Research Triangle Park, North Carolina where he worked until his retirement in 1994.

In December 1969 and early January 1970, Rodbell was working with a laboratory team that studied the effect of the hormone glucagon on a rat liver membrane receptor—the cellular discriminator that receives outside signals.

This GTP, he found, stimulated the activity in the guanine nucleotide protein (later called the G-protein), which, in turn, produced profound metabolic effects in the cell.