Ontogeny cannot be separated from mechanical forces. Cells are continuously subjected to different types of mechanical stimuli that convert into intracellular signals through mechanotransduction. As a member of the G protein-coupled receptor superfamily, adhesion G protein-coupled receptors (aGPCRs) have attracted extensive attention due to their unique extracellular domain and adhesion properties. In the past few decades, increasing evidence has indicated that sensing mechanical stimuli may be one of the main physiological activities of aGPCRs. Here, we review the general structure and activation mechanisms of these receptors and highlight the lesion manifestations relevant to each mechanosensitive aGPCR.