As reflected in rulings ranging from Trial Courts to the U.S. Supreme Court, our judiciary commonly views as “voluntary,” and admits into evidence, interrogation-induced confessions obtained under conditions entailing stressors sufficient to severely compromise or eliminate the rational decision making capacities and self-regulation abilities necessary to justify such a view. Such decisions reflect, and sometimes explicitly state, assumptions soundly contradicted by science regarding the capacity of normal suspects lacking mental defect to withstand such stressors as severe fatigue, sleep deprivation, emotional distress-- and aversive interrogation length, tactics and circumstances--and nevertheless resist the powerful pressures of the interrogation to self-incriminate. Notwithstanding excessive length and other severe interrogation-related stressors and tactics demonstrably associated with elicitation of false confessions, judges overwhelmingly admit confessions into evidence and juries overwhelmingly convict. In this review, we introduce the concept of “interrogation-related regulatory decline” (IRRD)—or decline in the self-regulation abilities necessary to resist the forces of influence inherent to interrogation. We review scientific evidence of the unexpected ease with which self-regulation abilities can be significantly compromised, with the hope that this evidence can (1) encourage more evidence-based objectivity, realism, clarity and specificity in the criteria for assessing voluntariness underlying admissibility decisions, (2) promote reforms aimed at prevention of interrogation practices entailing substantial risk of severe interrogation-related regulatory decline, and (3) encourage more scholarly research on acute sources of interrogative suggestibility.