The year 2015 marks the 10th anniversary of the release of two ICH Harmonised Tripartite Guidelines that have governed the cardiac safety regulatory landscape, more specifically the proarrhythmic cardiac safety landscape, since their release in May 2005. In this article, Snehal Kothari, MD, DM, FACC, FESC, Cardiologist and Senior Medical Director & Head of the Cardiac Safety Center of Excellence at Quintiles, Dilip R. Karnad, MD, FACP, FRCP (Glasg), Head of the Quintiles Cardiac Safety Services Research Team, Gopi Krishna Panicker, BHMS, PGDCR, Medical Writing Manager at Quintiles Cardiac Safety Services Research Team, J. Rick Turner, PhD, member of Quintiles’ Cardiac Safety and Cardiovascular Centers of Excellence, and Cardiac Safety Research Consortium’s Executive Committee give us an insight into cardiac safety investigations 10 years after ICH Guidance E14.