The endoplasmic reticulum (ER) is the main site for regulating protein synthesis and processing. Endoplasmic reticulum stress plays a role in regulating the osteogenic differentiation of stem cells and general osteoblasts. Bone marrow stromal cells (BMSCs, also known as bone marrow mesenchymal stem cells) are a group of progenitor cells that contain a small number of bone stem cells (SSCs) that rebuild cartilage, bone, stroma, and fat cells that support hematopoiesis and bone marrow. Therefore, due to their self-renewal and differentiation capabilities, they have become an important resource for researching regenerative medicine and tissue engineering treatment strategies. Exposure of osteoblasts to physical and biochemical stimuli facilitates rapid activation of early tissue repair processes in organisms. Therefore, the rational regulation of the induction conditions of osteoblasts has become a hot research topic. This article reviews the recent advances in the role of endoplasmic reticulum stress in the process of osteoblast differentiation.