Characterization and identification of phytoplankton species is important for understanding aquatic systems ecology. Whole genome sequencing of a phytoplankton species provides a detailed characterization of its gene content, giving insights into its metabolic pathways and physiology. Comparative genomics: the investigation into the similarities and differences of two or more organisms extends this characterization to an understanding of a species' environmental adaptation, ecology, and evolutionary history. This chapter provides an overview of comparative genomics, including a general workflow and the principles of data analysis. Concepts cover core, pan- and variable shell genomes, gene gain and loss, and strategies of genome evolution. As a model, we focus on the cyanobacteria, due to their small genome size, which provides an ease of study that does not extend to larger eukaryotes. A case study of the harmful bloom-forming cyanobacterium Raphidiopsis raciborskii is presented as an example of the investigation of intraspecific genomic diversity. Comparative genomics of R. raciborskii revealed that strains of this species complex have a high level of genetic variability, suggesting on-going genome adaptation via horizontal gene transfer and phage interactions.