The direct antiglobulin test (DAT; sometimes referred to as the "Coombs" test) continues to be one of the most widely used assays in laboratory medicine. First described about 70 years ago, it is elegantly simple in design, yet it is widely complex in its applications and interpretations, and it is prone to false-positive and false-negative results. The overall objective of our review is to provide practicing pathologists with a guide to identify situations when the DAT is useful and to highlight disease-specific shortcomings as well as general pitfalls of the test. To accomplish these goals, this review will discuss the following: (1) the history of the DAT, (2) how the test is performed in the clinical laboratory, (3) clinical situations for its use, (4) its interpretation, and (5) the pitfalls associated with DAT assays, including causes of false positivity.