•Neurons in the subthalamic nucleus (STN) switch from spike to burst firing during dopamine deficiency in Parkinsonism.•STN burst firing is formed by intrinsic neuronal membrane properties and is regulated by afferent neurotransmitters.•STN burst firing is directly correlated with motor symptoms in Parkinsonism, including tremor, rigidity and bradykinesia.•Treatments targeting at membrane properties or associated receptors can reduce burst firing in STN and improve Parkinsonism.•STN burst firing is a pathophysiological target in the treatment of Parkinson’s disease, especially in the context of DBS. Understanding the pathophysiological mechanism of Parkinson’s disease (PD) in the subthalamic nucleus (STN) has become a critical issue since deep brain stimulation (DBS) in this region has been proven as an effective treatment for this disease. The STN possesses a special ability to switch from the spike to the burst firing mode in response to dopamine deficiency in parkinsonism, and this STN burst is considered an electrophysiological signature of the cortico–basal ganglia circuit in the brains of PD patients. This review focuses on the role of STN burst firing in the pathophysiology of PD and during DBS. Here, we review existing literature on how STN bursts originate and the specific factors affecting their formation; how STN burst firing causes motor symptoms in PD and how interventions can rescue these symptoms. Finally, the similarities and differences between the two electrophysiological hallmarks of PD, STN burst firing and beta-oscillation, are discussed. STN burst firing should be considered as a pathophysiological target in PD during treatment with DBS.