The central concern of his career was how the natural world influences human behavior, and creates opportunities for political action to improve societal outcomes.
Masters began his career in political philosophy as a student of Leo Strauss at the University of Chicago.
The role of natural science in early political thought is also addressed in his 1996 book, Machiavelli, Leonardo and the Science of Power, and his 1998 book, Fortune is a River: Leonardo da Vinci and Niccolò Machiavelli's Magnificent Dream to Change the Course of Florentine History.
Later, Masters' research on biology and human behavior led to new epidemiological evidence regarding the behavioral impacts of neurotoxins, first on the consequences of lead poisoning, and then on the links between a common method of water fluoridation to elevated blood lead and a higher prevalence of violent crime, substance abuse and learning disabilities.
He was a founding member and served on the Executive Council of the Association for Politics and the Life Sciences, and led a multiyear consultancy on biology and politics for the U.S. Department of Defense in collaboration with anthropologist Lionel Tiger and neuroscientist Michael T. McGuire.