Randomized controlled trials (RCTs) are often considered the standard for defining the practice of evidence-based medicine. Taken alone, they are, however, often insufficient to guide clinical care. Randomized controlled trials are clearly the best method to determine whether interventions are efficacious. They have, however, numerous limitations which make them difficult to carry out or limit applicability to routine clinical practice. Although observational studies also have inherent limitations, they provide data which can help to further explain the results of randomized controlled trials. The use of observational studies to frame randomized trials can allow better application of randomized controlled trial results to individual patients and can thus help to optimize delivery of care, inform clinical practice and determine the need for further such trials.