European grapevine is a complex holobiont composed of two plant genomes, that of the scion (Vitis vinifera L.) and the rootstock (Vitis spp.), and a multitude of microbial genomes that collectively form the microbiome. The grapevine microbiome has been extensively described over the last decade, primarily using metabarcoding approaches. Unfortunately, metabarcoding data alone provide little information on microbial functions and outcomes of plant-microbe interactions. Here we review knowledge about the microorganisms that have a demonstrated influence, positive or negative, on the performance of the grapevine holobiont. Our review encompasses bacteria, filamentous fungi, yeasts, oomycetes and viruses. It covers aboveground and belowground microorganisms, including arbuscular mycorrhizal and ectomycorrhizal fungi. We focus on taxa and functions that protect the plant against pathogens and pests, promote growth, increase tolerance to abiotic stresses and highlight those involved in disease and decline. As the outcomes of plant-microbe interactions are labile, we examine the dynamics and functions of grapevine-microbiome interactions over both the plant lifetime and the plant evolutionary history, beginning with plant domestication. Based on the knowledge and gaps we identify, we suggest field sampling designs, culture-based experiments, molecular tools and theoretical analysis methods, including shotgun metagenomics and network models, that could be used in future research to uncover and leverage the full functional potential of the grapevine microbiome.