Twin-to-twin transfusion syndrome (TTTS) is a relatively unusual condition as genetically concordant twins develop phenotypically discordant features as a consequence of monochorionic placentation and the conjoined angioarchitecture. This chapter describes the underlying scientific basis for the development of the clinical picture of TTTS and discusses the interplacental vascular connections. Human hemochorial placentation involves vasculogenesis, the formation of blood vessels from non-vascular (hemangioblastic) precursors, in combination with angiogenesis, the remodeling of existing blood vessels to create new ones. The chapter provides the specific placental angioarchitecture in TTTS and explains the role angiogenic growth factors. Vascular endothelial growth factor (VEGF)-A and placental growth factor (PlGF) are shown to be potent angiogenic factors, being critical for placental angiogenesis, and also as permeability factors leading to vascular leakage. Objective ultrasound measurements of fetal cardiac function include: cardiothoracic ratio; ventricular chamber dimensions and freewall thickness; valvular regurgitation; and assessment of systolic and diastolic function.