Manual therapy is frequently used to treat low back pain (LBP), but evidence of its effectiveness is limited. One explanation may be sample heterogeneity and inadequate sub-grouping of participants in randomized controlled trials (RCTs) where manual therapy has not been targeted toward those likely to respond. Objectives: To determine the effectiveness of specific manual therapy provided to sub-groups of participants identified as likely to respond to manual therapy. Data sources: A systematic search of electronic databases of MEDLINE, EMBASE, CINAHL, and the Cochrane Central Register of Controlled trials (CENTRAL). Trial eligibility criteria: RCTs on manual therapy for participants identified as belonging to a sub-group of LBP likely to respond to manual therapy were included. Trial appraisal and synthesis methods: Identified trials were assessed for eligibility. Data from included trials were extracted by two authors independently. Risk of bias in each trial was assessed using the PEDro scale and the overall quality of evidence rated according to the GRADE domains. Treatment effect sizes and 95% confidence intervals were calculated for pain and activity. Results: Seven RCTs were included in the review. Clinical and statistical heterogeneity precluded meta-analysis. Significant treatment effects were found favouring sub-group specific manual therapy over a number of comparison treatments for pain and activity at short and intermediate follow-up. However, the overall GRADE quality of evidence was very low.