The existence of the type 1 insulin-like growth factor receptor (IGF-IR) had been surmised for a number of years, before it was cloned in 1986 by Ullrich et al. [1]. At that time, the IGF-IR was considered a poor relative of the insulin receptor (IR), with which it has a 70% homology [1], a sort of redundant receptor that the cells used when the IR was defective. The past 15 years have established the IGF-IR as an independent receptor, with overlapping, but different, functions from the IR and playing important roles in apoptosis, cancer, differentiation and even longevity. In this commentary, I will focus on the role of the IGF-IR in cancer, with special emphasis on its use as a possible target for therapeutic purposes. The role of the IGF-IR in cancer therapy rests on three fundamental observations (with subsequent variations) from the laboratories of Argyris Efstratiadis and ours. In 1993, Efstratiadis and co-workers [2] reported that the targeted disruption of the IGF-IR genes resulted in mice that, at birth, weighed 50% of the weight of wild-type littermates (see review in [3]). If the IGF-II genes were also deleted or inactivated (IGF-II is the only IGF growth factor in mouse embryos), the newborn mice were 30% in size. This finding was of the utmost importance because it established that: (1) The IGF-IR was (and still is) the only growth factor receptor whose deletion gives a growth phenotype in mouse embryos (other growth factor receptors, deleted, may give a lethal phenotype, but not a growth phenotype). (2) It indicated that the IGF-IR is responsible, in a non-redundant way, for 50% of the mouse embryo normal growth. (3) It also showed that 50% of normal growth is outside the jurisdiction of the IGF-IR and can be replaced by other