An important issue encountered in the historical artworks is the fading of the original colors because of their strong light sensitivity, infamously leading to the discoloration of masterworks even within an artist's lifetime. This phenomenon is clearly evidenced in many paintings of 19th century European impressionist artists, such as van Gogh, in particular when Organic Red Pigments (ORP) have been used. The identification of these ORP in historical paintings remains a main challenge because of (1) the generally low concentration of the original pigment remaining after an aging period of ca. 100 years, (2) the scarcity of the paint micro samples available for analysis and the difficulty of obtaining additional ones and (3) the complexity of degradation behavior in the presence of oxygen, inorganic semiconductor pigments, binding media or varnish. The objective of the RED-OPEN project is to develop a multi-analytical approach based on mass spectrometry and spectroscopic techniques (A) to understand their discoloration mechanism and (B) to identify their breakdown products, even if the original molecules are no longer present in the artworks. The successful completion of RED-OPEN will have a major impact in the understanding of the original artwork's appearance and will provide comprehensive and detailed knowledge of the progressive changes throughout the painting's history. RED-OPEN will generate knowledge that will help conservators and conservation scientists to understand the causes of discoloration and formulate mitigating actions, preserving invaluable art for future generations and further proposing a digital reconstruction of its originally intended appearance.