Blood vessels arise during early development and are essential for the formation and maintenance of larger tissues and organs. The vascular system regulates exchange of oxygen, nutrients, toxins and immune cells — the dysfunction of which can cause pathologies, as well as be consequent to the later stages of disease. Classical mouse models, genetics and histology, have provided significant knowledge to the field of vascular biology, in addition to recent advancements in diverse imaging modalities, single-cell approaches and computational modelling. Yet, there remain many open questions surrounding human vascular development and disease. Blood vessels present numerous research challenges due to their complex 3D geometry, and a strong coupling between biology and mechanics. Cutting-edge microfluidic and tissue engineering technologies offer a higher degree of control over design, system perturbations and characterisation. These advances also hold great promise for the development of relevant preclinical models, personalized and regenerative medicine.