Noonan syndrome – a common cause of congenital heart disease – is often associated with missense mutations in the protein phosphatase SHP-2. Interestingly, some types of leukaemia are associated with another subset of SHP-2 missense mutations. Here (p. 948), Frank Conlon and colleagues introduce SHP-2 that contains Noonan-associated mutations or juvenile myelomonocytic leukaemia (JMML)-associated mutations into Xenopus embryos to investigate how SHP-2 regulates heart development. Embryos that express SHP-2 containing Noonan-associated mutations have morphologically abnormal hearts, they report, whereas embryos that express SHP-2 containing JMML-associated mutations have normal hearts. The cardiac abnormalities caused by the Noonan-associated mutations are coupled with a delay or arrest in the cardiac cell cycle and with defective incorporation of cardiomyocyte precursors into the developing heart. Notably, these defects, which are caused by disruptions in the polarity of cardiac actin fibres and in F-actin deposition, can be rescued by inhibition of the Rho-associated, coiled-coil-containing protein kinase 1 (ROCK), which indicates that SHP-2 acts via ROCK to regulate the cardiac actin cytoskeleton during heart development.