Cell wall-deficient bacteria (CWDB) are pleomorphic bacterial forms. These atypical organisms may occur naturally or they can be induced in the laboratory. Their presence has been known about for over a century, but a definite link to clinical disease outcomes has not been demonstrated. A number of case reports and laboratory studies suggest some disease associations, however. Considerable controversy surrounds the true relevance of CWDB to disease; there is a widespread belief that they may represent a response by the walled organism to adverse extracellular conditions like antibiotic pressure. This review looks at studies published between 1934 and 2003, which were identified by Dialog DataStar using the key words 'cell wall deficient bacteria and clinical significance and infections' and by further scanning the reference list at the end of the papers retrieved. We conclude that the evidence for the clinical significance of CWDB in disease is not compelling.