In Drosophila, as in many other animals, EGFR-Ras signalling has multiple developmental roles from oogenesis to differentiation. In leg development, in particular, it has been described to be responsible for the establishment of distal leg fates in a graded manner. Here, we investigate the patterns of expression of activators of EGFR-Ras signalling, as well as some of the effectors, in order to better understand the patterning of the distal leg, and to investigate further roles of this signalling pathway. These patterns, together with genetic data obtained by different mutant conditions for EGFR-Ras members and transgene expression, suggest two rounds of signalling in leg development. Early, the EGFR ligand Vein is the main player in distal leg patterning, possibly supported later by another ligand activated by Rhomboid. Later, in a second wave of signalling when all the proximal-distal leg fates have been specified, domains of EGFR/Ras activation appear inside each leg segment to regulate Notch-mediated joint development, and also some organs such as tendons and sensory organs. This second wave relies on a ligand activated by Rhomboid. Developmental Dynamics 233:1496–1508, 2005. © 2005 Wiley-Liss, Inc.