Many therapies in neonatology persist without supportive evidence: some common therapies may actually be harmful. Evidence-based medicine is the "conscientious, explicit and judicious use of current best evidence in making decisions about the care of individual patients". The best available evidence, however, is not always sound or valid evidence. Sometimes, when faced with a collection of reports that do not constitute good evidence, attempts to choose the best evidence become pointless; in this case, a statement of no good evidence is preferable. There is a continuing problem with the place of usual practice in the hierarchy of evidence; usual practice generates experience with a particular practice but no reliable information regarding how the practice compares with alternative strategies. Although clinical and institutional inertia combined with a litigious practice environment tend to uphold current practice, the field of neonatology is ripe with examples of established therapies that were subsequently shown to be harmful. It is important to focus on important long-term outcomes and as much on the possibility of harm as on the chance of benefit, especially for new therapies, before they become routine practice. In the face of inadequate evidence, it is particularly important to avoid the temptation to institute treatment guidelines that inhibit further research. Patients are better served by guidelines that recommend only strategies that are supported by strong evidence and recommend further research when the evidence is inadequate.