I will discuss the systematic construction of globally consistent SU(5) GUT models on intersecting D7-branes in genuine Calabi-Yau orientifolds with O3- and O7-planes. Recent activities in local F-Theory model building have led to a new breaking of SU(5) to the Standard Model via hypercharge gauge flux. This mechanism relies on global properties of the ambient space rather than merely on local details of the GUT brane. After highlighting subtleties in the global consistency conditions and model building rules for SU(5) GUTs on intersecting branes, I discuss a type of geometry where this mechanism can be realized in a fully consistent string vacuum as opposed to a local quiver. This manifold is also interesting from the point of view of moduli stabilization. I will discuss the challenge of generating some of the Yukawa couplings non-perturbatively and present an explicit example that incorporates many phenomenologically appealing features, including the exact Standard Model spectrum and Higgs sector.