The coronavirus disease 2019 (COVID-19) pandemic is hitting the world’s most vulnerable people hardest, primarily the communities living in slums in the Global South. Lockdown, handwashing and social distancing are impossible privileges for many urban dwellers – measures which make structural inequities more visible, exacerbating racial, gender and class differences. There are many social determinants of health to explain these inequalities that trigger a high prevalence of infectious and chronic diseases. In Medellín (Colombia), it is a challenge to cope with this crisis, especially when the resources and aid provided by the government and institutions are limited. Yet, an organized social response is happening in some communes and slums, with high community participation, as a potentially effective key to control the pandemic. Once the emergency is over, communities in slums will have to face the social and economic reactivation, and effectively react to the multiple social and psychological consequences, new waves of COVID-19 or other pandemics.