Hemolysis affects many biochemical analyses, and when pronounced the result is replaced by an autoreply pointing out the hemolysis present. However, for proper treatment it is crucial to know whether hemolysis is due to sampling (in vitro) or is taking place in the patient (in vivo). At present, no consensus exists on how to help clinicians differentiate between the two. Clinical surveillance is still necessary, and a future challenge will be improving the dialogue between clinicians and clinical biochemists. This article reviews the benefits of doing so and suggests procedures to help differentiate.