DSM-5 lists 9 different symptoms for major depressive disorder and dictates that either “depressed mood” or “loss of interest or pleasure” should be present for diagnosis. Both are relatively high-level symptoms of the complex affecto-cognitive disease. However, the single most common behavioral paradigm and the gold standard animal (rodent) test for depression, the forced swim test (FST), measures a low-level mechanical feature that resembles “psychomotor retardation” observed in depression. This symptom refers to the slowing down of cognitive processes and an associated reduction in mobility. Likewise, the FST involves placing a rodent (mouse or rat) in a water-filled cylinder to measure its escape-related mobility over periods of immobility. Avoiding the term depression, this particular form of immobility observed in the FST was termed behavioral despair. Behavioral despair does not correlate with general mobility levels of the animal as measured in an open field test; and FST can reliably differentiate antidepressant treatments from other treatments that merely lead to increased mobility. It is therefore not a mere reflection of decreased physical energy or locomotion, but indicates the level of psychomotor activity of the animal. This review discusses the clinical significance and neurobiology of psychomotor retardation, and evaluates how FST, measuring this mechanical aspect of the disease, emerges as a reliable method and a critical step in antidepressant research.