This paper reviews the mechanisms governing high CO₂ acclimation. Acclimation of the photosynthetic apparatus and robustness of pH homeostasis in the cell, rapid shutdown of CO₂-concentrating mechanisms, and adjustment of membranes’ fatty acid composition are currently believed to be the key mechanisms governing microalgae’s tolerance to high CO₂ levels. The potential applications of high CO₂ tolerate microalgae in biological, bio-fuel development and other fields are analyzed. Screening species with high CO₂ tolerance and utilization of physiological and genetic engineering are effective ways to reduce CO₂ emissions and increase microalgae productivity of large-scale cultivation.