<p>Arteries serve primarily a biomechanical function. Critical insight into arterial structure, properties, and function thus derives from knowledge of mechanosensitive gene expression, associated microstructural organization, and biomechanical metrics such as compliance and vasoactive capacity. This review focuses on time-course changes in hemodynamic loads and associated changes in the transcriptional profile, mural composition, overall geometry, and mechanical properties of arteries during postnatal development, namely, from birth to a healthy adult. Although we examine the postnatal period, we allude to key findings during the prenatal period; although we draw on findings from multiple species and vessels, most data come from studies of the thoracic aorta in mice as an archetype vessel; and although we focus on normal development, we highlight four pathologic cases in which emergent homeostasis is compromised. Collectively, the data suggest that tissue-level mechanical homeostasis typically emerges following postnatal growth, with set-point values for multiple metrics dictating subsequent adaptations to changing hemodynamic loads in maturity, though with congenital defects, pathogenic variants, and disease conditions compromising homeostatic processes. Understanding the normal developmental program is essential for studying early-onset conditions, early surgical and pharmacological intervention, and ultimately aging as well as disease progression and its treatment in maturity.</p>