Recent advances in pluripotent stem cell biology now make it possible to generate human cardiomyocytes in vitro from both healthy individuals and from patients with cardiac abnormalities. This offers unprecedented opportunities to study cardiac disease development ‘in a dish' and establish novel platforms for drug discovery, either to prevent disease progression or to reverse it. In this review paper, we discuss some of the genetic diseases that affect the heart and illustrate how these new paradigms could assist our understanding of cardiac pathogenesis and aid in drug discovery. In particular, we highlight the limitations of other commonly used model systems in predicting the consequences of drug exposure on the human heart.