There is a myriad of microorganisms on Earth contributing to global biogeochemical cycles. In the surface ocean, the smallest microbes (picoplankton) are responsible for an important fraction of the total atmospheric carbon and nitrogen fixation. The ocean picoplankton encompasses both prokaryotes (bacteria and archaea) and tiny unicellular eukaryotes (protists). Despite their overall importance for the functioning of the biosphere, many questions remain unanswered on their biogeography, population dynamics, interactions, and evolution. Answering these questions is essential in the context of global change, as alterations of the ocean microbiome could impact the function of multiple ecosystems. In this thesis, we aim at reducing the knowledge gap on the above topics through the application of High-Throughput Sequencing (HTS) and genomic approaches, using data collected during the circumglobal Tara Oceans and Malaspina-2010 expeditions, as well as at the Gulf of Maine (North Atlantic), and two Northwestern Mediterranean coastal microbial observatories (BBMO and SOLA stations).