Founded in 1990 after originally being created as an art centre, Museo Reina Sofía is among the culminating events of the Spanish transition to democracy, recovering Pablo Picasso's Guernica as well as an outstanding representation of the international avant-gardes and neo-avant-gardes. In short, the founding of this museum means the recuperation of the experience of modernity previously missing from the Spanish context and the opportunity to try out new models of narration from a periphery that is neither lateral nor derivative, but is rather an entry way for new stories, historiographic models and artistic episodes that tip the balance of the orthodox canon of the main museums.

Therefore, the Museo Reina Sofía program is three-fold: on the one hand, rethinking the function of the museum today; on the other hand, analysing the mechanisms for mediation between the public and the institution; and finally, proposing new contexts and stories through the collection and exhibits that lead to a new notion of modernity.

The institution no longer considers its task to be simply the transmission of culture. Instead, it works with other agents and institutions, creating networks and alliances that strengthen the public sphere and position Museo Reina Sofía as a reference of prime importance in the geopolitical South. Similarly, the public is no longer conceived of as a homogenous and uniform multitude, but rather as a collective, multiple agent that questions, rejects and forms opinions, that builds, so to speak, its relationship with the Museum through the singularity of the artistic experience.

The building that houses Museo Reina Sofía is comprised of two parts: the museum's new wing, inaugurated in 2005 and built under the direction of the French architect Jean Nouvel, and the part that was originally built as the General Hospital, promoted by Philip II of Spain in the 16th century and later by Charles III of Spain. The original plans were drawn up by the engineer and architect Jose Agustín de Hermosilla in 1756 and continued by the Italian architect Francesco Sabatini during the second half of the 18th century. Today its appearance is far from the initial conception, due to the multiple modifications it has undergone despite the fact that it continued to be used as a hospital until 1968. It was then abandoned, leading to its deterioration during the subsequent years, until it was acquired by the Ministry of Education, in 1976, to be renovated and transformed into a cultural centre. In 1986, as a culmination of Spain's transition to democracy, the Reina Sofia Art Centre (Centro de Arte Reina Sofía) was created. Four years later it would become a National Museum (Museo Nacional Centro de Arte Reina Sofía), with the founding of the current museum.

The Museum's continual development in terms of its collections and activities led to the decision to study the possibility of increasing its floor area. The studies performed ended in 1999 and, following an international call for bids, the architect Jean Nouvel was chosen to direct the construction of the new building. His plans, in addition to meeting the needs expressed by the Museum, called for playing an active role in the neighbourhood, intervening and transforming the urban surroundings, while generating new services and a public square. The creation of the latter, made possible by the arrangement of new buildings and the southwest façade of the current Museum, gave a new space to the city.