During pregnancy, dramatic increases in uterine blood flow occur via a complex and integrated process of vascular enlargement and altered reactivity. The mechanisms underlying this adaptive process, which is essential for placental perfusion and normal pregnancy outcome are poorly understood. It is well established that insufficient adaptation is associated with pregnancy complications such as preeclampsia and intrauterine growth restriction. Our laboratory has been studying the pattern and extent of arterial remodeling during pregnancy by using the rat as an experimental model. In addition to the intact animal, we also employ a model in which unilateral uterine horn ligation (under anaesthesia) eliminates implantation in one uterine horn, resulting in an animal that is ‘half pregnant’. Although there may be some remodeling relative to nonpregnant controls, the marked differences between the implanted vs. nonimplanted horn indicate that a major part of the remodeling is due to local influences, such as increased shear stress due to the combination of a new low-resistance circulation (the placenta), and of vasodilatation of upstream vessels. Furthermore, there are localized differences in structure and reactivity between vessels that perfuse the myometrium vs. those that feed the placenta. In addition, I will present data that support the concept of venoarterial exchange as a contributing mechanism to vascular remodelling. This mechanism involves the secretion of mitogenic and/or vasoactive signals from the placenta into the venous effluent, and their transfer to the arterial side, which is facilitated by the anatomical proximity of veins and arteries in the uterine circulation of most mammals. In this regard, the potential role of VEGF and of PlGF in facilitating vessel dilation and growth will be discussed as a possible molecular pathway for gestational adaptation. Particular emphasis will be placed on VEGF-R1 (the Flt-1 receptor) in terms of signal transduction, and on the evidence that insufficient signaling due to an excess of a soluble form of this receptor (sFlt-1) is associated with preeclampsia, reduced vascular remodelling, and a significant reduction in fetal weight. The presentation will conclude with some discussion on the effects of hypertension, induced by nitric oxide inhibition, on vascular structure and reactivity, and on the beneficial fetal and vascular effects of supplementation with Sildenafil citrate (Viagra) to reinstate cGMP signalling in uterine vascular smooth muscle.