As molecular phenomena and chemical reactions typically involve more than one particle, non-covalent interactions (NCIs) of different molecules are often crucial when modeling such processes. With the increasing molecular complexity of the interacting systems, possible interaction motifs also become more diverse and harder to predict. Hence, an automated computational prediction of intermolecular geometries is desirable, ranging from two molecules up to large clusters consisting of many particles. For this, the efficiency and reliability of the xTB methods when simulating NCIs are a perfect match and allow an automated computational prediction of intermolecular geometries. This was realized with one of the novel features included in the xtb program package, namely the automated interaction site screening (aISS) algorithm, which generates dimers up to large clusters of interacting molecules fully automated. It combines the intermolecular force field xTB-IFF 156 for a fast and accurate screening of possible interaction sites with the GFN methods for reliable geometry optimizations. The aISS yields structures of similar quality as CREST by being 1-3 orders of magnitude faster. Combined with the broad parametrization of the underlying xTB methods, this allows to also treat systems with 1,000s of atoms almost regardless of the atomic composition. An example of this is shown in Fig. . The xTB-based docking was already applied to a variety of problems and molecular systems like the investigation of NCIs of supramolecular complexes, 157 ionic liquids, 158,159 metalorganic cages, 160 and nanobelts. In addition, xTB-based docking is employed in the context of explicit and microsolvation, e.g., with the QCG algorithm. 162 This hybrid clustercontinuum approach generates clusters of solutes solvated by solvent molecules that are em-bedded in implicit solvation models like GBSA or ALPB. It was, for example, successfully employed to model solvation in the context of reaction mechanisms, 163 conformational analysis, and spectroscopic properties.