Motivated by the tantalizing excesses recently reported in the di-photon invariant mass spectrum at the LHC, we scrutinize some implications of scalar di-photon resonances in high energy proton-proton collisions. In particular, indications of a large width impose several challenges for model building. We show how calculability and unitarity considerations severely limit possible perturbative realizations of such a signal and propose a simple criterion that can be adapted to any renormalizable model. Furthermore, we discuss correlations between a di-photon excess and precision observables, including the anomalous magnetic and electric dipole moments of quarks and leptons, neutral meson oscillations and radiative flavor changing neutral current mediated decays of heavy leptons and hadrons. We find that existing searches and measurements significantly constrain the possibilities for a scalar resonance decaying into final states involving Standard Model fermions. We propose future search strategies which could elucidate some remaining currently unconstrained decay channels and discuss possible correlations between the di-photon excess and several recently reported flavor anomalies, showing that the latter can be addressed in a new incarnation of a gauged U(1) ′ model, with the di-photon resonance being the physical remnant of the U(1) ′ -breaking field.