Although vertebrates look bilaterally symmetrical, their internal organs are placed asymmetrically. In some organisms, Ca2+ signalling and cilia function in the embryonic node have been implicated in the establishment of this left-right (LR) asymmetry. Now, Schneider and colleagues report that Ca2+ fluxes also have a conserved function in LR patterning before node formation (see p. 75). In zebrafish embryos, Kuppfer's Vesicle (KV), which is derived from the dorsal forerunner cells (DFCs), is homologous to the node in mice and chicks. The researchers show that endogenous Ca2+ is released in the DFC region after the onset of gastrulation but before KV and cilia formation. The inhibition of this early Ca2+ release, the researchers report, disrupts KV formation, which alters the expression of asymmetric markers and the asymmetric placement of internal organs. Other experiments indicate that β-catenin inhibition is the target of this early Ca2+ signalling. Finally, the researchers identify DFC-like cells in Xenopus embryos and provide evidence that early Ca2+ signalling is a conserved feature of LR patterning.