Empirical evidence has revealed various factors that contribute to the development and maintenance of Internet abuse. The aim of this paper was to analyze, on a sample of Spanish adolescents, the relationship between Internet abuse and: (1) Personal and interpersonal risk factors, including social skills in both virtual and real-life contexts; (2) Drug use. A total of 814 high school students aged between 13 and 17 participated in this study, and were divided into two groups: Internet Abusers (IA = 173) and Non-Internet Abusers (NIA = 641). Questionnaires were used to analyze Internet and drug use/abuse, as well as social skills, in virtual and real contexts. Various interpersonal risk factors (family and group of friends) were also assessed. IA showed a more severe pattern of Internet and drug use, as well as poorer social skills in both contexts. Moreover, their groups of friends appeared more likely to become involved in risky situations related to Internet and drug abuse. Both IA and NIA showed more adaptive social skills in the virtual context than in the real one. There is a need for further research to build on these findings, with a view to designing specific preventive programs that promote responsible Internet use.