Paintings are complex multi-layered systems made of organic and inorganic materials. Several factors can affect the degradation of paintings, such as environmental conditions, past restoration works and, finally, the type of painting technique and the art materials used over the centuries. The chemical–physical characterization of paintings is a constant challenge that requires research into and the development of novel analytical methodologies and processes. In recent years, solvents and water-related issues in paintings are attracting more attention, and several studies have been focused on analyzing the interaction between water molecules and the constitutive materials. In this study, recent applications applying different NMR methodologies were shown, highlighting the weakness and the strength of the techniques in analyzing paintings. In particular, the study of water and its diffusive interactions within wall and oil paintings was performed to prove how the portable NMR can be used directly in museums for planning restoration work and to monitor the degradation processes. Furthermore, some preliminary results on the analysis of varnishes and binders, such us linseed oil, shellac, sandarac and colophony resins, were obtained by 1H HR-MAS NMR spectroscopy, highlighting the weakness and strengths of this technique in the field of conservation science.