Study Design. A systematic review. Objective. The aim of this review was to evaluate the effectiveness of motor control exercise (MCE) in patients with nonspecific low back pain (LBP). Summary of Background Data. MCE is a common form of exercise used for managing LBP. MCE focuses on the activation of the deep trunk muscles and targets the restoration of control and coordination of these muscles, progressing to more complex and functional tasks integrating the activation of deep and global trunk muscles. Methods. We conducted electronic searches of CENTRAL, MEDLINE, EMBASE, five other databases, and two trials registers from their inception up to April 2015. Two independent review authors screened the search results, assessed risk of bias, and extracted the data. A third reviewer resolved any disagreement. We included randomized controlled trials comparing MCE with no treatment, another treatment, or as a supplement to other interventions in patients with nonspecific LBP. Primary outcomes were pain intensity and disability. We assessed risk of bias using the Cochrane Back and Neck (CBN) Review Group 12-item criteria. We combined results in a meta-analysis expressed as mean difference and 95% confidence interval. We assessed the overall quality of the evidence using the GRADE approach. Results. We included 32 trials (n = 2628). Most included trials had a low risk of bias. For acute LBP, low to moderate quality evidence indicates no clinically important differences between MCE and spinal manipulative therapy or other forms of exercise. There is very low-quality evidence that the addition of MCE to medical management does not provide clinically important improvements. For recurrence at one year, there is very low-quality evidence that MCE and medical management decrease the risk of recurrence. For chronic LBP, there is low to moderate quality evidence that MCE is effective for reducing pain compared with minimal intervention. There is low to high-quality evidence that MCE is not clinically more effective than other exercises or manual therapy. There is very low to low quality evidence that MCE is clinically more effective than exercise and electrophysical agents (EPAs) or telerehabilitation for pain and disability. Conclusion. MCE is probably more effective than a minimal intervention for reducing pain, but probably does not have an important effect on disability, in patients with chronic LBP. There was no clinically important difference between MCE and other forms of exercises or manual therapy for acute and chronic LBP.