Research with children is globally subjected to specific safeguards. There are natural aspects related to their cognitive development and their capacity to assent and consent to their participation as subjects. Developing countries, and overall, countries with high levels of inequality due to socio-economic reasons create additional concerns for investigators and research ethics committees members. Several Latin American countries are emerging from decades of political unrest, civil wars and different levels of corruption—situations that are reflected in the number of children living on the street. These children are prone to being used in petty crime, sexual abuse and human trafficking. All research carried out with this particular vulnerable population must adhere to strict ethical safeguards. Although there is no evidence that these minors could be used as subjects in clinical trials, all studies that are to be conducted with these children must respond to specific hypotheses that could ameliorate or even improve their living conditions. The uneven capabilities of local research ethics committees and lax regulatory framework in some Latin American countries are of further concern to this population.