Forty years ago, Lundberg introduced the concept of the brain-to-brain loop for laboratory testing. In this concept, in the brain of the physician caring for the patient, the first step involves the selection of laboratory tests and the final step is the transmission of the test result to the ordering physician. There are many intermediary steps, some of which are preanalytic, ie, before performance of the test; some are analytic and relate to the actual performance of the test; and others are postanalytic and involve transmission of test results into the medical record. The introduction of this concept led to a system to identify and classify errors associated with laboratory test performance. Errors have since been considered as preanalytic, analytic, and postanalytic. During the past 4 decades, changes in medical practice have significantly altered the brain-to-brain loop for laboratory testing. This review describes the changes and their implications for analysis of errors associated with laboratory testing.