The first generation of in silico hERG models have focused on key driving forces for hERG/ligand binding: basicity and lipophilicity. While reducing basicity and lipophilicity are typically the first line approaches to eliminating hERG blocking activity, in many programs these are not feasible approaches because basicity and lipophilicity are frequently necessary for achieving good pharmacokinetics or primary target binding. Thus for the second, generation of in silico hERG models, a focus on understanding the more subtle aspects of hERG binding is necessary. Thus, the focus of this review is on extracting ideas, either qualitative or quantitative, from the various modeling efforts as to how hERG activity might be eliminated or diminished beyond simply reducing basicity and lipophilicity. In addition, several areas where key questions around hERG binding have not been adequately addressed by in silico work are highlighted.