The present work explored the role of family rejection on the sexual behavior of Latino gay men under the guidance of the minority stress model. Family rejection was analyzed as a distal stressor, self-esteem as a proximal stressor, and unprotected sex as the outcome. The hypotheses were tested using regression, mediation, and multiple regression of secondary data from the Latino men who have sex with men (MSM) community involvement project. The results suggested that family rejection is a weak predictor of low self-esteem and engaging in receptive unprotected sex with more partners. Low self-esteem did not mediate the relationship between family rejection and sexual behavior. These findings were obtained during a post hoc analysis using a continuous outcome variable. Using unprotected sex as a dichotomous variable was not useful to detect a statistically significant correlation. The results suggested that the mixed findings in the previous literature might be due to differences in the instrumentation of the variables. The present work ends with recommendations for future research and policy about collecting and handling data to study sexual risk behavior in Latino gay men. An additional recommendation is the need to redefine unprotected sex under the light of the new preventive therapies for HIV and the current decline in condom use. The study highlighted the need for a multilevel approach to the health disparities affecting Latino gay men and the need for structural changes in federal and state policies to facilitate public health and clinical interventions that can lead to social change.