LBP remains an enormous burden for workers, employers and society as a whole. Despite all efforts in studying work-related risk factors for developing LBP, interventions targeting these risk factors to prevent LBP have not been cost-effective. Even with adequate implementation strategies for these interventions, no effect in the reduction of incident LBP on group level could be detected. Genetic and biological de- terminants probably also play a major role in the aetiology of LBP, next to existing work-related risk factors. This is in accord with evidence showing that physical exercise has a primary preventive effect on LBP. For secondary prevention, it seems that there are more opportunities to cost-effectively intervene in reducing the risk of long-term sickness absence due to LBP. Starting at the earliest moment possible with proper assessment by a well-trained clinician of risk factors related to the individual, the underlying mechanisms of the LBP, and also factors related to the workplace may increase the effectiveness of RTW management. For LBP with more chronic sickness absence, various interventions have a small but clin- ically relevant and cost-effective effect in reducing sickness-absence duration. The uptake of these effective interventions in managing LBP with chronic sickness absence not only by clinicians, but also by policymakers and insurers remains a big problem. More research in how to overcome these barriers in various policy-specific environments, and with regard to proper financing of RTW management, may help to increase the implementation of cost-effective interventions.