Despite having available treatments for most cardiac diseases there is an increasing need for more specific and effective therapies. To help drug developers advance smoothly in this process, it is important to decrease the translational gap that is leading to high attrition rates and costs. Human-induced pluripotent stem cell (iPSC) technology is increasingly utilised to develop disease models that reliably mimic the diversity of patient pathogenicity and cardiac disease severity in vitro. Phenotypic screening based on iPSC models represents a big opportunity to make cardiac drug discovery more time and cost-effective by increasing the translational power of preclinical candidates. Noelia Muñoz-Martín and Elena Matsa at Ncardia, review common challenges and goals for drug developers and how the latest innovations in iPSC technology are contributing to efficiently advancing cardiac drug discovery.