Lateral ankle sprain is a common orthopedic injury with a very high recurrence rate in athletes. After decades of research, it is still unclear what contributes to the high recurrence rate of ankle sprain, and what is the most effective intervention to reduce the incident of initial and recurrent injuries. In addition, clinicians often implement balance training as part of the rehabilitation protocol in hopes of enhancing the neuromuscular control and proprioception of the ankle joint. However, there is no consensus on whether the neuromuscular control and proprioception are compromised in unstable ankles. To reduce the prevalence of ankle sprains, the effectiveness of engaging balance training to enhance the neuromuscular control and proprioception of the ankle joint is also questionable. Core tip: Lateral ankle sprain is a common orthopedic injury with a high recurrence rate. However, there is no consensus on whether neuromuscular control and proprioception are compromised in unstable ankles, and whether proprioception training can reduce initial and recurrent ankle injuries. The purpose of this review is to discuss the etiology and intervention of initial and recurrent ankle sprains, focusing on the role of neuromuscular control and proprioception at the ankle joint. This review can provide clinicians the knowledge of constructing better examination protocols and rehabilitation programs for individuals with the unstable ankle.Hung Y. Neuromuscular control and rehabilitation of the unstable ankle. World J Orthop 2015; 6(5): 434-438 Available from: URL: