Drug addiction is a multifactorial disorder resulting from the complex interaction between biological, environmental and drug-induced effects. Generally, stress is a well-known risk factor for the development of drug addiction and relapse. While most of the research focuses on risk factors that increase the vulnerability to drugs of abuse, recent studies are focusing on the areas of strength/positive coping approaches that can increase resistance to drugs of abuse. In this review, we concentrate on resilience, seen as a dynamic process, which can allow individuals to positively adapt within the context of a specific risk for psychiatric illness. Here, we discuss the effects of social stress in animal models on drug use, particularly cocaine. In contrast, we suggest social interaction reward when available as an alternative to drug use as an approach contracting negative stress effects and increasing resistance to drug use. Indeed, interventions, which aim at enhancing resilience to stress through the facilitation of social interaction and the enhancement of social support, could be particularly effective in helping people cope with stress and preventing drug use problems or relapse. Finally, understanding the neurobiological mechanisms underlying protective factors such as social interaction reward should provide the basis for future evidence-based interventions targeting substance abuse and stress-related pathologies.