This document summarizes the results achieved by Caritas Spain, the Spanish Red Cross, Fundación ONCE and Fundación Secretariado Gitano within the European Social Fund Operational Programme “Fight against Discrimination” between the years 2000 and 2015. During this period, these four organizations have assisted 850,000 people in vulnerable and exclusion situations and have contributed to provide employment for 230,000. Moreover, these entities have promoted more than 1,000 entrepreneurship and self-employment initiatives. All this has been possible thanks to the support of the Spanish Government, to the multiplying effect of own resources combined with the European Social Fund and also to the creation of an extensive supporting network of companies and institutions of all kinds. This Programme is a unique initiative in Europe, which has been widely awarded and recognized in the past years, and which the European Commission has repeatedly highlighted as an example of good practice and social innovation. The external evaluation of this Programme, which has invested 700 million € and that counted with specialized human capital consisting of 1,600 professionals and 29,000 volunteers, has proven that the use of these resources is good social investment. For each euro invested, the return has been of 1,4 €. Investing in labor and social inclusion of vulnerable groups not only contributes to the targets of Europe 2020 Strategy of increasing the level of employment and reducing poverty and social exclusion, but also helps to increase public income through taxes and social security contributions, involves saving in social expenditure and promotes economic growth. In the current programming period 2014-2020, the funds Provisions set the requirement of allocating 20% of the European Social Fund resources to vulnerable and excluded groups. The experience gained by these four entities and their capacity to respond to these people’s needs, positions them as key actors in the implementation of the new Operational Programme for Social Inclusion and Social Economy.