Photosynthetic organisms have evolved various acclimatory responses to high-light (HL) conditions to maintain a balance between energy supply (light harvesting and electron transport) and consumption (cellular metabolism) and to protect the photosynthetic apparatus from photodamage. The molecular mechanism of HL acclimation has been extensively studied in the unicellular cyanobacterium Synechocystis sp. PCC 6803. Whole genome DNA microarray analyses have revealed that the change in gene expression profile under HL is closely correlated with subsequent acclimatory responses such as (1) acceleration in the rate of photosystem II turnover, (2) downregulation of light harvesting capacity, (3) development of a protection mechanism for the photosystems against excess light energy, (4) upregulation of general protection mechanism components, and (5) regulation of carbon and nitrogen assimilation. In this review article, we survey recent progress in the understanding of the molecular mechanisms of these acclimatory responses in Synechocystis sp. PCC 6803. We also briefly describe attempts to understand HL acclimation in various cyanobacterial species in their natural environments.