He is best known for his discoveries that reveal the inner workings of an important family of G protein-coupled receptors, for which he was awarded the 2012 Nobel Prize for Chemistry with Brian Kobilka.

[3][4] After graduating from the Bronx High School of Science in 1959,[5] he attended Columbia College from which he received a Bachelor of Arts in chemistry in 1962.

[10] Lefkowitz is among the most highly cited researchers in the fields of biology, biochemistry, pharmacology, toxicology, and clinical medicine according to Thomson-ISI.

[6] In 2021, Lefkowitz published a memoir entitled A Funny Thing Happened on the Way to Stockholm: The Adrenaline-Fueled Adventures of an Accidental Scientist.

The book describes Lefkowitz's early life, training as a physician, and tenure in the United States Public Health Service (the "Yellow Berets" of the NIH), which began as a means of fulfilling his draft obligation during the Vietnam War but ultimately ignited a lifelong passion for research.

Upon publication in February 2021, the book was named as "New & Noteworthy" by The New York Times[13] and "one of the week's best science picks" by Nature.