Conventional wisdom touts the benefits of “treating yourself” as a means of maintaining psychological and physical health. Evidence suggests, however, that prosocial—rather than self-focused—behavior is linked with benefits to well-being and physical health. In two longitudinal experiments, we contrasted the effects of prosocial behavior (i.e., doing acts of kindness for others or for the world) and self-oriented behavior (i.e., doing acts of kindness for oneself). In our first study (N = 473), we found that the two types of prosocial behavior led to greater increases in psychological flourishing and positive emotions than did self-focused and neutral behavior. In our second study (N = 159), prosocial behavior directed towards specific others improved a leukocyte gene expression profile known as the Conserved Transcriptional Response to Adversity (CTRA). Together, these findings suggest that prosocial behavior improves psychological flourishing and can causally impact immune gene expression in ways that may help explain previously observed advantages associated with social ties.