Vascular endothelial growth factor A (VEGF-A) and its cognate receptors are central to the regulation of angiogenesis in both physiological and pathological states. In cancer, local tumour hypoxia stimulates VEGF-A synthesis and VEGF-A levels are subsequently elevated in a wide variety of cancers. VEGF-A thus has enormous potential as a diagnostic and prognostic biomarker of disease status. The justification of VEGF-A as a biomarker has not yet been achieved, primarily due to our lack of understanding of its multiple splice variants and its spatio-temporal distribution. Here we highlight how recent technological advancements and kinetic-dynamic modelling could be used towards validating VEGF-A as a biomarker for clinical use in human disease management.