Pharmacological challenge tests of the serotonergic system have extensively been used during the past 20 years and new tests are in development. It is of crucial importance to standardize challenge tests to ascertain that observed variability is due to the state of the challenged system and not caused by variability of the test itself. This is even more important now that challenge tests increasingly are used in complex studies (e.g. in combination with neuroimaging and in large population studies with repeated tests over time). The Guideline for Good Clinical Practice may be of great help in the standardization of these tests. This is a recently developed guideline for pharmaceutical drug-development, which increasingly is used as a reference for all research in humans. To exemplify the possible usefulness of this approach, we apply it to meta-chlorophenylpiperazine, one of the most commonly used drugs in serotonergic challenge tests. We conclude that much can be learned from the development of this particular challenge. In the discussion, we address general issues that emerged from this review and their relevance to the development of future challenge tests.