The potential and application of X-ray absorption spectroscopy (XAS) for structural investigations of organic–inorganic hybrid materials, with a special emphasis on systems consisting of inorganic building blocks (clusters) embedded into polymer backbones, is extensively reviewed. In the first part of the paper, the main features of organic–inorganic hybrid materials, their classification, the synthetic approaches for their preparation, and their applications are concisely presented, whereas the particular issues related to their characterization are discussed in more detail. In the second section of the paper, the principles and the theoretical background of the XAS method, including experimental design, data reduction, evaluation, analysis, and interpretation are described and discussed. Examples of potentialities of the method for the short-range structural investigation of inorganic nanostructures in hybrids are provided, and the state-of-the-art in the field of hybrid materials is reviewed. In the third part, six different case studies belonging to our past and present experience in this field are presented and discussed, with a particular focus on their XAS investigation.