Background: With a growing number of users, social networking sites have been the subject of numerous recent studies, but little investigation has been given to their problematic use. Objectives: Our main objective was to study the relationship between psychopathological variables (i.e., personality traits, depressive and anxiety symptoms, and stress) and problematic Facebook and Twitter use. Participants and method: A sample of 1068 Internet users (Mage = 26.64; SD = 9.5) has been recruited online. Participants completed scales exploring problematic Facebook and Twitter use, and psychopathological variables. Results: Problematic Facebook and Twitter use were predicted by different pathological personality traits, regrouped in clusters in our study. Depressive and anxiety symptoms were also predictive of problematic Facebook and Twitter use but only stress explained problematic Facebook use. Gender differences have been observed. Discussion: This study highlights the relationship between depression, anxiety, stress, pathological personality traits, and problematic Facebook and Twitter use. Significant differences have been retrieved between these two uses and their relationship to psychopathology. Future research should also explore the causal relationship between social networking sites use and psychopathology and consider gender.