Modern viticulture is undergoing a paradigm shift, transitioning from a plant-centric view to the holobiont concept, which considers the grapevine (Vitis vinifera L.) and its associated microbiota as a single co-evolved functional unit. This review synthesizes current knowledge on the grapevine holobiont, identifying the drivers of microbial assembly (genotype, environment, management) and their functional implications for plant health and wine quality. We discuss the pillars of plant health, defining disease as a state of dysbiosis rather than merely the presence of a pathogen. Special attention is given to the spatial compartmentalization of the microbiome, from the gating mechanisms of the rhizosphere to the transient diversity of the anthosphere. Furthermore, we highlight the methodological evolution from culture-dependent techniques to Next-Generation Sequencing (NGS) and the emerging role of MALDI-TOF MS as a rapid, cost-effective tool for real-time monitoring. Finally, we propose a roadmap for microbiome-assisted viticulture that utilizes synthetic microbial communities (SynComs) and hologenomic breeding to enhance resilience against climate change.