In the current study, we examined the mediating role of internalized heterosexism in the link between heterosexist discrimination and psychological distress among 361 lesbian, gay, and bisexual (LGB) persons who completed an online survey. We also examined the potential moderating role of meaning in life (both search for and presence of) in the links between heterosexist discrimination and psychological distress and between the heterosexist discrimination and internalized heterosexism. As such, we examined a moderated mediation model. We hypothesized that search for meaning would play an exacerbating role and presence of meaning would play a buffering role in these relationships. Results revealed internalized heterosexism mediated the heterosexist discrimination and psychological distress link. In addition, presence of meaning moderated and buffered the heterosexist discrimination-psychological distress link. Findings from the moderation analyses also revealed that the direct effect of heterosexist discrimination on internalized heterosexism and the conditional indirect effect of heterosexist discrimination on psychological distress were contingent on search for meaning such that these relationships were only significant among LGB persons with moderate to high levels of search for meaning. Finally, search for meaning did not moderate the heterosexist discrimination–psychological distress link and presence of meaning did not moderate the heterosexist discrimination–internalized heterosexism link.