IUGR can develop, either in response to a reduced IGP or in response to a deficient transplacental supply of O2 and nutrients. Particularly, insight in the pathogenesis of extrinsic IUGR is important for the clinician to offer him tools for a more causal treatment. Extrinsic IUGR is usually preceded by a gradually developing uteroplacental insufficiency. Uteroplacental hypoperfusion may represent the common starting point for extrinsic IUGR and maternal systemic symptomatology (PIH, (pre)eclampsia). In addition, it may be the common endpoint of two different (subclinical) pathways: defective trophoblast differentiation ("primary") and decompensation of early-pregnancy circulatory maladaptation ("secondary"). From a theoretical point of view, the primary pathway may develop at a slower rate. Therefore, the primary pathway is more likely to result in extrinsic IUGR. In contrast, the secondary pathway assumes decompensation of an initially maladapted maternal circulation. This implies a highly variable rate of development and with it, severity of clinical symptomatology. It also indicates that the the pathogenesis, eventually leading to manifest vascular disease, is superimposed on a pre-existent inadequacy in maternal hemodynamics, renal function and/or volume homeostasis. It is understood that intertwining of these two pathways is common. Unfortunately, our current knowledge, about placentation and the concomitant early-pregnancy adjustments is poor. Current research of trophoblast differentiation and of the concomitant maternal end-organ effects in normal and pathologic pregnancy, is likely to increase our understanding of the first-trimester phenomena preceding IUGR soon.