This article has a twofold purpose: to describe the social and economic situation in the countries of the Central American subregion prior to the coronavirus disease (COVID-19) pandemic and to provide a comparative analysis of the macroeconomic policies introduced by the governments of these countries in response to this health crisis. As a central part of that analysis, it looks at the main structural policy challenges for the enhancement of social protection and reactivation of production activity and employment to be met by these countries during and after the pandemic. The need for a national compact around a new development agenda is explored, with special emphasis on external elements that should be coupled with national policies, such as regional coordination, international cooperation and finance, and a restructuring of financial and lending institutions.