This study examined the interrelations among shame-proneness, guilt-proneness, internalized heterosexism (IH), and problematic substance use among 389 gay, lesbian, and bisexual men and women. Problematic alcohol and drug use were positively related to shame-proneness and negatively related to guilt-proneness. Bisexuals reported riskier substance use behaviors, lower levels of guilt-proneness, and higher levels of IH than gay men and lesbians. Furthermore, study findings indicated that shame and IH are related. Additional investigations of these associations would supplement current understandings of sexual minority stress and advance the development of substance-related intervention and prevention efforts targeting sexual minorities.