Summary Objective Craniosacral therapy (CST) is an alternative treatment approach, aiming to release restrictions around the spinal cord and brain and subsequently restore body function. A previously conducted systematic review did not obtain valid scientific evidence that CST was beneficial to patients. The aim of this review was to identify and critically evaluate the available literature regarding CST and to determine the clinical benefit of CST in the treatment of patients with a variety of clinical conditions. Methods Computerised literature searches were performed in Embase/Medline, Medline® In-Process, The Cochrane library, CINAHL, and AMED from database start to April 2011. Studies were identified according to pre-defined eligibility criteria. This included studies describing observational or randomised controlled trials (RCTs) in which CST as the only treatment method was used, and studies published in the English language. The methodological quality of the trials was assessed using the Downs and Black checklist. Results Only seven studies met the inclusion criteria, of which three studies were RCTs and four were of observational study design. Positive clinical outcomes were reported for pain reduction and improvement in general well-being of patients. Methodological Downs and Black quality scores ranged from 2 to 22 points out of a theoretical maximum of 27 points, with RCTs showing the highest overall scores. Conclusion This review revealed the paucity of CST research in patients with different clinical pathologies. CST assessment is feasible in RCTs and has the potential of providing valuable outcomes to further support clinical decision making. However, due to the current moderate methodological quality of the included studies, further research is needed.