Psychophysiological approaches to personality have made significant progress in recent years, partly as a spin-off of technological innovation (e.g., functional neuroimaging) and partly as a result of an emerging theoretical consensus regarding the structure and biology of basic processes. In this field, Jeffrey Gray's influential psychophysiological theory of personality - now widely known as Reinforcement Sensitivity Theory (RST) owes much to Pavlov, who devoted a large proportion of his later life to personality differences and their implications for psychiatry. In this article, we trace the influence of Pavlov on Hans Eysenck's and Jeffrey Gray's work, and then provide a brief description of RST in order to highlight some of the central problems - as well as some tentative solutions - in the psychophysiology of personality. Specifically, the importance of theory in personality research is stressed by the contrast of Gray's theoretically driven model with less fertile atheoretical (i.e., exploratory-inductive) approaches. The fecundity of RST, which has been in continual development over a period of thirty years, is discussed in the light of Karl Popper's views on the nature of science, especially the formulation of the 'problem situation', which sets up the theoretical and operational conditions under which hypotheses may be challenged and tested to destruction. In this respect, we see the truth of Lewin's [Lewin, K., 1951. Field theory in social science: selected theoretical papers. In: Cartwright, D., (Ed.). Harper & Row, New York] famous phrase, "There is nothing so practical as a good theory".