Research on the health of sexual and gender minority populations has been predominantly framed within the context of health disparities and social stress. Findings produced from research employing health disparities and social stress frameworks have spurred significant advancements in basic and applied science on sexual and gender minority health, and have been useful in arguing for the removal of discriminatory social policies. Critiques of these frameworks suggest their dominant role in the research literature risks an artificially narrow portrayal of relevant lived experience, and further pathologizes and stigmatizes sexual and gender minority populations. Methodological challenges involve the measurement of explanatory variables within comparative research designs. By taking stock of these benefits and challenges, suggestions can be made for future research designed to maximize the benefits of health disparities and social stress frameworks for understanding and improving the health of sexual and gender minority populations in ways that are responsive to critiques while recognizing variability in lived experience.