Assessing whether an acute phase response (APR) is present or not presents a complex problem to clinicians and researchers. Part of this complexity is the nature of the process itself. As a result, choosing what method to use is crucial and fraught with pitfalls. Increasingly evident is the fact that the APR is constantly present in all creatures. The problem then is, what level of the APR are we proposing to investigate? The answer to this, a decade or so ago, was easily decided by the relative insensitivity of the assays then available; we simply could not detect low levels of the markers of inflammation. In the last few years, however, C-reactive protein (CRP) assays of increasing sensitivity have shown that, in fact, the continuum of CRP values extends essentially to zero and we are able to assay down to these extremely low levels with assurance. As a result, we again have to face the decision of what constitutes a significant level of inflammation; what is the clinical cut-point? Recent information indicates that even low levels of inflammation, as assessed by sensitive assays, can provide information relevant to specific and serious disease. In other words, there would appear that there is no level of APR which does not place us at some risk for illness. Although this represents a major contribution to our level of understanding, remaining is our inability to specify where this low level process exists; cystitis, gingivitis, bronchitis, post-exercise inflammation, early malignancy, or evolving coronary artery disease.