The growth factor receptor bound (Grb) 7 family of src homology (SH)2 domain-containing adapter proteins contains three members: Grb7, 10 and 14 (Daly 1998, Han et al. 2001). An observation that has intrigued researchers in the field for a decade is the close similarity between the central regions ofGrb7 and a Caenorhabditis elegans cell migration protein, Mig10 (Stein et al. 1994, Manser et al. 1997). This conserved region encompasses a Ras-association (RA) and a pleckstrin homology (PH) domain. The recent characterization of two mammalian orthologues of Mig10, Rap1-GTP interacting adapter molecule (RIAM)/proline-rich EVH1 ligand (PREL)1 and Lpd (Lamellipodin) now sheds light on the relationship between the Grb7 family and Mig10 (Lafuente et al. 2004, Krause et al. 2004, Jenzora et al. 2005). Sequence and domain structure comparisons reveal that two related protein families have arisen during evolution: the Grb7 family, and the newly-termed Mig10/RIAM/Lpd (MRL) family (Lafuente et al. 2004) (Figure 1A). Since Grb7 family orthologues are absent from C. elegans, it is likely that the corresponding gene families evolved from a common ancestral gene encoding a Mig10-like protein. In this review, we describe how the addition of different protein modules or motifs to a common core domain structure has given rise to two families of adapter proteins with distinct molecular connectivities and signalling functions (Figure 1B).