Functional cardiomyocytes can be efficiently derived from human pluripotent stem cells (hPSCs), which collectively include embryonic and induced pluripotent stem cells. This cellular platform presents exciting new opportunities for development of pharmacologically relevant in vitro screens to detect cardiotoxicity, validate novel drug candidates in preclinical trials and understand complex congenital cardiovascular disorders, to advance current clinical therapies. Here, we discuss the progress and impediments the field has faced in using hPSC-derived cardiomyocytes for these in vitro applications, and highlight that rigorous protocol optimisation and standardisation, scalability and automation are remaining obstacles for the generation of pure, mature and clinically relevant hPSC cardiomyocytes.