The structure of atomic nuclei depends on the interactions of its constituents, protons and neutrons. These interactions play a key role in the development of configuration mixing and in the onset of collectivity and deformation, in changes to the single particle energies and magic numbers, and in the microscopic origins of phase transitional behavior. Particularly important are the valence proton-neutron interactions which can be studied experimentally using double differences of binding energies extracted from high-precision mass measurements. The resulting quantities, called delta V-pn, are average interaction strengths between the last two protons and the last two neutrons. Focusing on the Z=50-82, N=82-126 shells, we have considered a number of aspects of these interactions, ranging from their relation to the underlying orbits, their behaviour near close shells and throughout major shells, their relation to the onset of collectivity and deformation, and the appearance of unexpected spikes in delta V-pn values for a special set of heavy nuclei with nearly equal numbers of valence protons and neutrons. We have calculated spatial overlaps between proton and neutron Nilsson orbits and compared these with the experimental results. Finally we also address the relation between masses (separation energies), changes in structure and valence nucleon number.