The inter-relationships between the Big Five personality traits, self-esteem, and compulsive buying are supported by strong empirical evidence. What is yet unknown is to what extent self-esteem can channel the influence of personality traits on compulsive buying. The main objective of this study is to explore the possible mediating role of self-esteem in the link between the Big Five personality traits and compulsive buying. Path analysis results, using a sample of 487 university students, generally confirm the suitability of the proposed model in which self-esteem mediated the effects of the Big Five personality traits (neuroticism, extraversion, agreeableness, openness to experience, and conscientiousness) on compulsive buying. Moreover, a direct effect of neuroticism and conscientiousness on compulsive buying was found. Finally, based on the finding that self-esteem acts as a necessary filter in the analysis of the five factors-compulsive buying relationship, several action-oriented guidelines for the prevention or intervention of this behavioral problem are suggested.