One of the prime applications made possible with the introduction of the xTB methods is the large scale screening of molecule structures. This computational efficiency for high throughput calculations in combination with an efficient approach, like metadynamics, to explore the potential energy surface, has been realized with CREST. The CREST program provides the de facto standard for sampling conformer ensembles. This has enabled the exploration of a broader chemical space, facilitated by the extensive parameterization of the xTB methods, leading to publications spanning a wide range of applications. This comprises, for example, drug design and delivery, 76 catalyst design and reaction pathway studies, molecular switches, and peptide dynam-ics. A more detailed overview of CREST and its applications can be found in the recently published software review. Aside from CREST, there are several alternative conformer generation tools found in the literature that have been used in combination with xtb. Popular choices are: AB-Cluster based on the artificial bee colony algorithm, Molclus program 83 used in combination with the Multiwfn wave-function analyzer, conformational search module of Hy-perChem, ETKDG method 86 implemented in RDKit library, Confab toolkit, the autodE pipeline and XTBDFT. There are also some projects which prefer to search for conformers manually or semi-manually by means of molecular simulation techniques. Even though conformer search is crucial and an integral part of structural investigations, the system size that can be treated is certainly limited. For systems with thousands of atoms, performing such analysis is not computationally feasible on modern CPU architectures. In such cases, xtb still serves as a valuable energy minimization tool, as GFN2-xTB was used for geometry optimization in nearly one-fifth of the publications discussed in Section 6. Typical systems include but are not limited to, proteins, polypeptides, 97 metal-organic frameworks, nanotubes, large non-covalently bound complexes, 101-103 and porous liquids.