In most animals, the placement of the internal organs has left-right (LR)asymmetry with an invariant handedness. How handedness – whether an organ lies on the right or the left – is initiated during development is unclear. On p. 5731,Bergmann and co-workers identify GPA-16, a component of a heterotrimeric G protein, as the first C. elegans protein that affects handedness. LR asymmetry in C. elegans becomes evident sometime between the four-and six-cell stages, and is determined by a shift in the orientation of specific mitotic spindles. The researchers show that loss-of-function of GPA-16 affects spindle orientations during the third cleavage and nearly randomises handedness among the resulting adult worms. Heterotrimeric G proteins are also involved in the control of asymmetric cell division, and on p. 5717, Tsou et al. show that G-protein signalling interacts with LET-99, a protein whose localisation pattern is dependent on polarity cues, to regulate spindle orientation, and thus asymmetric cell division, in early C. elegansembryos.