The cardiovascular system demonstrates left-right (LR) asymmetry: most notably, the LR asymmetric looping of the bilaterally symmetric linear heart tube. Similarly, the orientation of the aortic arch is asymmetric as well. Perturbations to the asymmetry have been associated with several congenital heart malformations and vascular disorders. The source of the asymmetry, however, is not clear. Cell chirality, a recently discovered and intrinsic LR asymmetric cellular morphological property, has been implicated in the heart looping and vascular barrier function. In this paper, we summarize recent advances in the field of cell chirality and describe various approaches developed for studying cell chirality at multi- and single-cell levels. We also examine research progress in asymmetric cardiovascular development and associated malformations. Finally, we review evidence connecting cell chirality to cardiac looping and vascular permeability and provide thoughts on future research directions for cell chirality in the context of cardiovascular development and disease.