Background. Clinical prediction rules (CPRs) for treatment selection in musculoskeletal conditions have become increasingly popular. Purpose. The purposes of this review are: (1) to critically appraise studies evaluating CPRs and (2) to consider the clinical utility and stage of development of each CPR. Data Sources. Pertinent databases were searched up to April 2009. Studies aiming to develop or evaluate a CPR for treatment response in musculoskeletal conditions were included. Two independent reviewers assessed eligibility and extracted methodological data, stage of development, and effect size information. Study Selection/Data Extraction and Synthesis. Eighteen studies, evaluating 15 separate CPRs, were included. Fourteen CPRs were at the derivation stage, and all CPRs had been evaluated using a single-arm trial design, thus it is not possible to determine whether the CPRs identify prognosis (regardless of treatment) or specifically response to treatment. The CPR at the validation stage investigated spinal manipulative therapy (SMT) for low back pain and had been evaluated in 2 separate well-conducted randomized controlled trials. The first trial demonstrated a clinically meaningful effect of the SMT CPR; the additional effect from SMT in patients "positive-on-the-rule" was 15 Oswestry disability units at week 1 and 9 units at week 4. The second trial showed that the CPR did not generalize to a different clinical setting, including a modified treatment. Limitations. Due to differences in methods of reporting and journal publication restraints (eg, word count restrictions), some quality assessment items may have been completed in the included studies, but not captured in this review. Conclusions. There is, at present, little evidence that CPRs can be used to predict effects of treatment for musculoskeletal conditions. The principal problem is that most studies use designs that cannot differentiate between predictors of response to treatment and general predictors of outcome. Only 1 CPR has been evaluated within an RCT designed to predict response to treatment. Validation of these rules is imperative to allow clinical application.