The U.S. system for determining liability for environmental disease requires plaintiffs to demonstrate that the defendant was the legal cause of their illnesses. The determination of cause takes place in an adversary setting. Both sides in the dispute present evidence about causation to a lay judge or jury, who is responsible for deciding whether the defendant is legally responsible. In injury cases this generally means providing evidence of a specific, concrete event or condition that gave rise to the plaintiff's harm. Environmental disease usually presents a very different picture, one in which there is considerable uncertainty about the relationship between exposure to toxic substances and the plaintiff's disease. Scientific evidence about this uncertain link is often an essential part of the case.

The reliance on scientific evidence appears to present almost insurmountable problems of proof of causation to the plaintiff. The law requires the plaintiff to demonstrate that, without the defendant's action, the harm would not have occurred. This strict requirement appears incompatible with the substantial scientific uncertainty about the cause of many environmental diseases. A second attribute of legal causation is that it is based on common experience, and is easily understood by lay citizens who are likely to be the final arbiters of causation. Scientific explanations of environmental disease causation, on the other hand, may not draw on common experience and may not have the intuitive appeal necessary to convince a lay decision-maker. Because scientific evidence of causation is difficult for a lay judge or jury to understand, and because of the adversary use of experts with very different opinions about causation, it might be expected that plaintiffs would have a great deal of difficulty demonstrating causation in environmental liability cases.

However, the U.S. legal system appears to have accommodated to the plaintiff's difficulty in meeting the formal burden of persuasion. The courts allow juries considerable leeway in using their own experience and beliefs to determine causation, as long as there is some scientific evidence to support the plaintiff's contention.

The U.S. environmental disease liability system has been criticized by some for plaintiffs' difficulty in proving causation and by others because plaintiffs can win cases without evidence that would be convincing to a scientist. This has led to suggestions for reform, including: (1) attempts to alter rules governing the introduction of scientific evidence, (2) altering the burden of persuasion to make the legal definition of cause more consistent with the inherent scientific uncertainty in these cases, (3) the use of formal presumptions to aid in establishing legal causation, and (4) replacing or supplementing the existing environmental disease liability system with an administrative compensation system. Those proposing reforms do not always appear to recognize that there is already considerable flexibility in the existing system.