Twitter is one of the world’s most popular social networking sites, yet gaps remain in our knowledge about the psychology of its users. The current studies sought to fill these gaps by examining whether the Big Five and Dark Triad personality traits predicted differences between Twitter users and Facebook-only users, motives for using Twitter, the frequency of tweeting about 4 topics—intellectual pursuits, personal achievements, diet/exercise, and social activities—and how much they liked to read tweets about these topics. Study 1 found that Twitter users (N = 346) were higher in openness (i.e., intellect and creativity) than Facebook-only users (N = 268). In Study 2, a preregistered replication, Twitter users (N = 255) were not only higher in openness than Facebook-only users (N = 248), but they were also more Machiavellian. In both studies, Twitter users who were higher in openness were more strongly motivated to use Twitter for career promotion, and in turn, they tweeted more frequently and most liked to read tweets about intellectual pursuits. Narcissists were more strongly motivated to use Twitter for career promotion, social connection, and attention-seeking, and in turn, they tweeted more frequently and most liked to read tweets about personal achievements and diet/exercise. On average, participants most liked to read tweets about intellectual pursuits and least liked tweets about diet/exercise. We discuss the implications of these findings for tailoring one’s tweets to retain followers and for drawing the boundary conditions when extrapolating from Twitter-based “big data” to larger populations.