Background: Structural determinants of health are gaining recognition as being a prominent force in influencing risk of infectious diseases. Both HIV and Chagas disease are strongly influenced by structural inequities and represent significant burdens of communicable disease in terms of disability-adjusted life years in Latin America. Objective: Using the risk environment framework as a guide, the primary objective of this dissertation is to explore physical, social, and individual factors associated with increased risk for two diseases of interest: HIV and Chagas disease. Specific aims of each manuscript chapter are: To test structural factors associated with smoking methamphetamine among a cohort of female sex workers (FSWs) in Tijuana, Baja California, Mexico (Chapter 2); To determine the prevalence of sexual risk behaviors, HIV, and syphilis and to analyze variables associated with inconsistent condom use among casual partners among a sample of substance using migrants residing at the Mexico/Guatemala border (Chapter 3); To determine the seroprevalence of Chagas disease in regional and international migrant populations at the Mexico/Guatemala border and assess correlates of infection including migration path, sociodemographic, and socioeconomic variables (Chapter 4). Methods: Chapter 2 uses data from a longitudinal cohort study of FSWs in Tijuana (Mapa de Salud). Chapters 3 and 4 use data from a cross-sectional study among international and regional migrants at the Mexico/Guatemala border (Cruzando Fronteras). Chapter 4 also uses data from a UC MEXUS dissertation grant on Chagas disease. Results: We found that FSWs and migrants who used substances were at heightened risk for HIV via their substance use and sexual risk behaviors. The key social and physical structural factors associated with those risk behaviors were neighborhood, housing, and access to condoms. For Chagas disease, key physical structural factors were impoverished housing and being born in a rural area. Conclusions: The risk environment framework was a useful way to conceptualize the hypothesized relationships between structural factors and individual risk behaviors. This dissertation highlights multiple areas of structural vulnerability in order to suggest potential intervention points and shed greater light on the spaces in which our participants live.