Semaphorins family consists of more than 20 proteins, categorized into 8 subclasses. Semaphorins play critical roles in neural development, immune response, and bone metabolism. Rheumatoid arthritis (RA) is a disease which shows abnormality in immunity and bone homeostasis. Therefore, semaphorins are suggested to be relevant to RA. Here, we described the role of semaphorins in bone metabolism and the association with semaphorins and RA which are found by basic and translational research.