Individual-level preventive interventions are also needed for individuals currently suffering from mental health problems resulting from stigma-related stress. Unfortunately, although LGB individuals seek mental health services at greater rates than heterosexuals (Cochran et al., 2003), there are currently few, if any, evidence-based treatments that address their unique mental health issues (Cochran, 2001). A recent meta-analysis (Marshal et al., 2008) noted that none of the intervention guidelines published by the principal medical and public health institutions provides information for health-care providers on how to prevent substance use in sexual minority youth, despite their increased risk. Marshal and colleagues (2008) note that this paucity of guidelines regarding modifiable targets for intervention is directly related to the fact that existing research has rarely considered mediators of the association between sexual orientation and substance use. The uniqueness of the integrative mediation framework advanced in this paper is that it identified processes that are both modifiable through existing interventions and that appear to be psychosocial sequelae of stigma-related stress.