Abstract: This paper briefly introduces the basic principle of magnetic resonance (MR) and the challenges limiting its sensitivity.The physical mechanism behind the production of hyperpolarized 129Xe to enhance the MR signal is explained. Due to its high lipid solubility in biological tissues and large chemical shift to neighbor environments, hyperpolarized 129Xe has been employed in lung and brain MR imaging. The developments in these research fields are reviewed, and representative advances in clinical trials are described as well. Furthermore, the prospects of ultrasensitive MR with hyperpolarized 129Xe molecular sensors are discussed, and future applications and directions of hyperpolarized 129Xe MR in biomedicine are outlined