INTRODUCTION: In recent years, robot-assisted gait training (RAGT) has been proposed as therapy for balance and gait dysfunctions in people with multiple sclerosis (PwMS). Through this systematic review, we aimed to discuss the impact of RAGT on balance and gait outcomes. Furthermore, characteristics of the training in terms of robots used, participants characteristics, protocols and combined therapeutic approaches have been described.EVIDENCE ACQUISITION: As part of the Italian Consensus on robotic rehabilitation "CICERONE" a systematic search was provided in PubMed, the Cochrane Library and PEDro to identify relevant studies published before December 2019. Only randomized control trials (RCT) involving RAGT for PwMS were included. PEDro scale was used to assess the risk of bias and the Oxford Center for Evidence-Based Medicine (OCEBM) was used to assess level of evidence of included studies.EVIDENCE SYNTHESIS: The search on databases resulted in 336 records and, finally, 12 studies were included. RAGT was provided with Exoskeleton in ten studies (6-40 session, 2-5 per week) and with end-effector in two studies (12 sessions, 2-3 per week) with large variability in terms of participants' disability. All the exoskeletons were combined with bodyweight support treadmill and movement assistance varied from 0% to 100% depending on participants' disability, two studies combined exoskeleton with virtual reality. The end-effector speed ranged between 1.3 and 1.8 km/h, with bodyweight support starting from 50% and progressively reduced. In seven out of twelve studies RAGT was provided in a multimodal rehabilitation program or in combination with standard physical therapy. There is level 2 evidence that RAGT has positive impact in PwMS, reaching the minimally clinically importance difference in Berg Balance Scale, six-minute walking test and gait speed.CONCLUSIONS: In available RCT, RAGT is mostly provided with exoskeleton devices and improves balance and gait outcomes in a clinically meaningful way. Considering several advantages in terms of safety, motor assistance and intensity of training provided, RAGT should be promoted for PwMS with severe disability in a multimodal rehabilitation context as an opportunity to maximize recovery.