Background: Patients with MS commonly report problems with walking, balance, fatigue and visual disturbances. These symptoms can appear suddenly, they have a variable course and they differ in severity. Among the frequently encountered symptoms in MS, fatigue remains the most challenging one, majorly altering the quality of life. It affects up to 80% ofMS patients. Aim of Study: The aim of this systematic review was to examine the effectiveness of physical therapy interventions for fatigue in multiple sclerosis patients. Material and Methods: Thecurrent study was made on patients with multiple sclerosis aged ³18 years. We searched the PubMed, Pedro, Cochrane and goggle scholar web site from inception up till now. Systematic review of randomized controlled trials, the intervention used was physical therapy interventions as a group programs. Nine studies were selected according to inclusive and exclusive criteria and descriptive analysis were conducted due to heterogeneity. Results: Seven studies assessed fatigue by physical therapy interventions in multiple sclerosis patients. There was very high heterogeneity in fatigue severity scale among studies (n=7 studies, n=941 participants, p < 0.00001; I2=95%). There was significant overall effect between exercise therapy group and control group in fatigue by fatigue severity scale (SMD= –1.24; 95% CI, –1.38 to –1.10; p < 0.00001), two studies assessed fatigue by physical therapy interventions in multiple sclerosis patients. There was very high heterogeneity in modified fatigue impact scale among studies (n=2 studies, n= 131 participants, p=0.004; I2=88%). There was significant overall effect between exercise therapy group and control group in fatigue by modified fatigue impact scale (SMD= –0.57; 95% CI, –0.93 to –0.22; p=0.002) three studies assessed fatigue by physical therapy interventions in multiple sclerosis patients. There was very high heterogeneity in visual analogue scale among studies (n=3 studies, n=234 participants, p <0.00001; I2=98%). There was significant overall effect between exercise therapy group and control group in fatigue by visual analogue scale (SMD=0.96; 95% CI, 0.66 to 1.27; p < 0.00001), four studies assessed fatigue by physical therapy interventions in multiple sclerosis patients. There was no heterogeneity in multiple sclerosis quality of life-54 among studies (n=4 studies, n=177 participants, p=0.62; I2=0%). There was significant overall effect between exercise therapy group and control group in fatigue by multiple sclerosis quality of life-54 (SMD=0.35; 95% CI, 0.05 to 0.65; p=0.02). Sensi-tivity analysis showed that fatigue assessed by multiple sclerosis quality of life-54 was non-significant by excluding one trial at a time from pooled effects to determine whether any one study was particularly influential. No significant or change in heterogeneity (I2=0%) among including four studies was observed after removal one study according to sensitivity analysis matrix. Conclusion: The current level of evidence supports the effectiveness of physical therapy interventions for reducing fatigue in multiple sclerosis patients.