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In Guided Bone Regeneration (GBR) materials and techniques are essential to achieve the expected results. Thanks to their properties, blood clots induce bone healing, maturation, differentiation and organization. The preferred material to protect the clot in Guided Bone Regeneration is the titanium foil, as it can be shaped according to the bone defect. Furthermore, its exposition in the oral cavity does not impair the procedure. We report on five clinical cases in order to explain the management of blood clots in combination with titanium foil barriers in different clinical settings. Besides being the best choice to protect the clot, the titanium foil represents an excellent barrier that is useful in GBR due to its biocompatibility, handling, and mechanical strength properties. The clot alone is the best natural scaffold to obtain the ideal bone quality and avoid the persistence of not-resorbed granules of filler materials in the newly regenerated bone. Even though clot contraction still needs to be improved, as it impacts the volume of the regenerated bone, future studies in GBR should be inspired by the clot and its fundamental properties.