The precautionary principle asserts that the burden of proof for potentially harmful actions by industry or government rests on the assurance of safety and that when there are threats of serious damage, scientific uncertainty must be resolved in favor of prevention. Yet we in public health are sometimes guilty of not adhering to this principle. Examples of actions with unintended negative consequences include the addition of methyl tert-butyl ether to gasoline in the United States to decrease air pollution, the drilling of tube wells in Bangladesh to avoid surface water microbial contamination, and villagewide parenteral antischistosomiasis therapy in Egypt. Each of these actions had unintended negative consequences. Lessons include the importance of multidisciplinary approaches to public health and the value of risk-benefit analysis, of public health surveillance, and of a functioning tort system-all of which contribute to effective precautionary approaches.