By the 1950s Linus Pauling was certainly the premier structural chemist and probably the premier chemist of his time. His work was capped by the Nobel Prize, awarded in 1954 "for his research into the nature of the chemical bond and its application to the eludication of the structure of complex substances."

The chemistry prize was based on forty years' work, during which he developed a distinctive style as well as stellar results. During the late 1920s and early 1930s, Pauling devised new ways of discovering the molecular structures of complex substances. Three central concepts guided this work: Quantum mechanics could be used to describe and predict atomic binding; the structures of simple molecules could be used in building-block fashion to predict the structures of more complex ones; and, perhaps most important, chemical structure could be used to determine chemical behavior. This body of work resulted in the 1939 publication of The Nature of the Chemical Bond, a book that taught a generation of chemists to think about chemical structure. It is one of the most-cited texts in the history of science.

Beginning in the late 1930s and continuing into the 1950s, Pauling's laboratory began determining the molecular structures of amino acids, the building blocks of proteins. By the early 1950s, Pauling used his model-building approach to solve the large-scale structures of many proteins, an enormous advance in molecular biology, although his attempt to determine the structure of DNA failed. Nonetheless, in a brilliant series of articles, Pauling established the basis for understanding protein structure. In 1954 he was awarded the Nobel Prize for chemistry.

Nine years later, Pauling was awarded the Nobel Peace Prize for his work against the use and proliferation of nuclear weapons. This was also based on long-standing work. After World War II, appalled by the devastation at Hiroshima and Nagasaki and spurred on by his wife, Ava Helen, Pauling joined other scientists in expressing concerns about bomb testing and agitating for civilian oversight. The U.S. government responded by putting him under FBI surveillance, canceling his research grants, refusing him a passport, and stripping him of his security clearance. He was accused of being a Communist and was vilified in the press.

Medical research and political activism overlapped during the 1950s as Pauling began devoting much of his time to the debate on radioactive fallout. He marshaled and presented evidence that the seemingly trivial increases in background radiation caused by fallout could, in the aggregate, cause significantly greater numbers of birth defects and cancer worldwide. He denounced the testing of nuclear weapons, publicly took on the counter-claims of the Atomic Energy Commission, and debated bomb-test advocates like Edward Teller. He circulated anti-bomb petitions, led demonstrations, gave innumerable speeches and wrote a book, No More War! Pauling's work, which contributed significantly to the development of the first nuclear test ban treaty of the Cold War period, was based in great part on health concerns.

Being awarded the 1954 chemistry Nobel Prize gave great impetus to his peace work, providing him with the public forum from which he could continue his crusade. In 1957-1958 he and his wife gained worldwide fame by gathering the signatures of 11,000 scientists on a petition asking for an end to nuclear weapons testing, which they then presented to the United Nations. This was an important step in turning the tide of public opinion. On the day that the first nuclear test ban treaty went into effect, October 10, 1963, Pauling received the news that he was to be awarded the Nobel Peace Prize.