Lipid flippases are integral membrane proteins that use ATP hydrolysis to power the generation of phospholipid asymmetry between the two leaflets of biological membranes, a process essential for cell survival. Although the first report of a plant lipid flippase was published in 2000, progress in the field has been slow, partially due to the high level of redundancy in this gene family. However, recently an increasing number of reports have examined the physiological function of lipid flippases, mainly in Arabidopsis thaliana. In this review we aim to summarize recent findings on the physiological relevance of lipid flippases in plant adaptation to a changing environment and caution against misinterpretation of pleiotropic effects in genetic studies of flippases.