We previously showed that three genes that normally guide embryonic development (abbreviated GMT) can directly reprogram cardiac fibroblasts, which are structural cells in the heart, into beating heart muscle-like cells called induced cardiomyocytes (iCMs) in vitro and in vivo. We found that, in addition to GMT, two additional genes, ESRRG and MESP1, were required to directly reprogram human fibroblasts into iCMs in vitro, and an additional two genes, MYOCD and ZFPM2, further improved reprogramming. Similar to mouse GMT-reprogrammed in vitro iCMs, human iCM reprogramming was stable and displayed comparable quality of reprogramming.