Angiography with iodinated contrast agents is bound up with the risks of contrast-induced nephrotoxicity and hypersensitivity, which led to the idea of using carbon dioxide (CO2) gas as a negative contrast medium to eliminate these drawbacks. During the last decade, refinements and experiences have proved carbon dioxide digital subtraction angiography (CO2-DSA) to be an accurate, safe, and clinically promising vascular imaging modality, with the advantages of no hypersensitivity and no nephrotoxicity as well as minimal patient discomfort. In this article, we have reviewed the history, physical and chemical aspects, techniques, and pathophysiologic changes with the use of CO2-DSA as well as some clinical trials. Applications of CO2 gas in vascular interventions and other imagings, and the advantages and limitations of using CO2 gas in DSA are also discussed.