John Cacioppo passed away in 2018, leaving a legacy of profound methodological, theoretical, and inferential contributions to social neuroscience. This paper serves as an introduction to the nine articles that comprise this special issue in honor of John Cacioppo's work in social neuroscience. Although he made many contributions to psychology, here we briefly review four milestones in Cacioppo's career that had important implications specifically for the development of social neuroscience today: (1) an early research focus on cardiovascular and facial EMG measurement, (2) the training of others, (3) the importance of sound inference, and (4) the definition of social neuroscience. In sum, we argue that John Cacioppo envisioned social neuroscience as having multiple levels of explanation and requiring multiple kinds of physiological evidence. It is not all just the brain!