The presented empirical study among a sample of n = 256 participants addressed the relationship between consumers' need for uniqueness and their reactions to web-based personalized advertising. Drawing on regulatory focus theory, we argue that the consumers' need for uniqueness dimensions creative choice and similarity avoidance may relate to promotion and prevention regulatory orientations, respectively. Accordingly, we hypothesized that creative choice and similarity avoidance would differentially predict self-reported approach and avoidance behavior toward personalized advertising. These direct relationships were further expected to be mediated by subjective evaluations of personalized advertising (i.e., perceived value and irritation). In line with these hypotheses, we found that creative choice predicted approach behavior through increased web-based personalized advertising value, whereas similarity avoidance predicted avoidance behavior through increased irritation. Creative choice also predicted decreased irritation, which in turn was related to decreased approach behavior. In sum, the results suggest that the consumers' need for uniqueness dimensions should not be investigated as a composite, as they seem to reflect different regulatory orientations and are therefore likely to evoke different affective, cognitive, and behavioral responses.