Pdgfrα+ stromal cells are a group of cells specifically expressing Pdgfrα, which may be mentioned with distinct names in different tissues. Importantly, the findings from numerous studies suggest that these cells share exactly similar biomarkers and properties, show complex functions in regulating the microenvironment, and are critical to tissue regeneration, repair, and degeneration. Comparing the similarities and differences between distinct tissue-resident Pdgfrα+ stromal cells is helpful for us to more comprehensively and deeply understand the behaviors of these cells and to explore some common regulating mechanisms and therapeutical targets. In this review, we summarize previous and current findings on Pdgfrα+ stromal cells in various tissues and discuss the crosstalk between Pdgfrα+ stromal cells and microenvironment.