Heart-forming organoids (HFOs) derived from human pluripotent stem cells are a complex, highly structured in vitro model of early heart, foregut and vasculature development. In the human embryo, these tissues emerge in close proximity to each other and rely on signal exchange for proper development. HFOs represent a potent tool for various applications, including teratogenicity assessment as well as organ development and disease studies. Expanding on the first description of the HFO model in Nature Biotechnology (featured on the cover in June 2021; Link), Lika Drakhlis, Santoshi Biswanath Devadas and Robert Zweigerdt have now published an advanced protocol for HFO generation and analysis applying a number of complementary methods, including detailed descriptions of “do’s and don’ts” required for success. You can find the original article in the journal “Nature Protocols” featuring HFO generation on the cover page of the December 2021 issue (Link).