Medically unexplained symptoms (MUS) commonly present across the board in medical specialties and are often challenging to treat. Our objective was to assess the efficacy for cognitive-behavior therapy (CBT) in MUS. Electronic search of databases was carried out for published controlled trials in English language peer-reviewed journals from inception till August 2016. Effect sizes for the trials were computed using standardized mean difference, and I(2) test was used to assess sample heterogeneity. Pooled mean effect sizes were derived using a random-effects model.