Mobility is a key determinant of HIV/sexually transmitted infection (STI) transmission dynamics in Asia and Africa. Scant data exist regarding its dynamic impacts on HIV/STI risk in Central America and Mexico. Our objective was to critically review the epidemiology and social and structural context of HIV/STI risk among mobile populations in Central America and Mexico. Eligible articles were published in English or Spanish between January 1, 2000 and August 31, 2010; conducted in Central America or Mexico; specified the mobile population included; and described primary research. 2045 records were screened, 275 articles reviewed, and 22 studies included. Mobility is associated with increased HIV risk behaviors, though it also may increase preventive behaviors. Among mobile groups in Central America and Mexico, social isolation, the socio-economic impacts of displacement, gender inequalities, and stigma/discrimination shape HIV risk. Epidemiologic research and multi-level interventions that target and engage vulnerable groups in transit stations are recommended.