Picocyanobacteria are the smallest and most ancient photosynthetic autotroph known to date with wide distribution and abundant density in the oceans. As the major contributor to primary production, marine picocyanobacteria have significant impacts on global carbon cycles and ocean food web. Given the picocyanobacterial genome streamlining and remarkable diversity during the long process of evolution, studies of their molecular ecology provide key scientific basis for relationships among genotypic, phenotypic and ecological variations, as well as for insights of biotic adaptation evolution in the context of environmental requirements. With the application of newly molecular biotechniques over recent years, our reports on the molecular ecology of marine picocyanobacteria have not only revealed their features of temporal-spatial distribution, fine distribution patterns of genetical subgroups and environmental factors controlling their variations, but also explored their adaptation mechanism derived from information about genomic functions and expressions. Accessing the further progresses in genomic information of these organism, coupled with the advances in the environmental adaptation mechanisms on molecular level given valuable information on distribution characteristics, it would be able to simulate the regulatory and metabolic network of picocyanobacteria in high resolution integrated into the framework of ecosystem model which is the main focus on the future perspectives in molecular ecology of picocyanobacteria.