Gastrointestinal decontamination has been practiced for hundreds of years; however, only in the past few years have data emerged that demonstrate a clinical benefit in some patients. Because most potentially toxic ingestions involve agents that are not toxic in the quantity consumed, the exact circumstances in which decontamination is beneficial and which methods are most beneficial in those circumstances remain important topics of research. Maximum benefit from decontamination is expected in patients who present soon after the ingestion. Unfortunately, many overdose patients present at least 2 hours after taking a medication, when most of the toxin has been absorbed or has moved well into the intestine, beyond the expected reach of gastrointestinal decontamination. Decontamination probably does not contribute to the outcome of many such patients, especially those without symptoms. However, if absorption has been delayed or gastrointestinal motility has been slowed, activated charcoal may reduce the final amount absorbed. The use of activated charcoal in these cases may be beneficial and is associated with few complications. Therefore, administration of activated charcoal is recommended as soon as possible after emergency department presentation, unless the agent and quantity are known to be nontoxic, the agent is known not to adsorb to activated charcoal, or the delay has been so long that absorption is probably complete. The use of gastric emptying in addition to activated charcoal has generated intense debate. Several large comparative studies have failed to demonstrate a benefit of gastric emptying before activated charcoal. Because complications of such 2-step decontamination include a higher rate of intubation, aspiration, and ICU admission, gastric emptying in addition to activated charcoal cannot be considered the routine approach to patients. However, there are several infrequent circumstances in which the data are inadequate to accurately assess the potential benefit of gastric emptying in addition to activated charcoal: symptomatic patients presenting in the first hour after ingestion, symptomatic patients who have ingested agents that slow gastrointestinal motility, patients taking sustained release medications, and those taking massive or life-threatening amounts of medication. These circumstances represent only a small subset of ingestions. In the absence of convincing data about benefit or lack of benefit of gastric emptying for these patients, individual physicians must act on a personal valuation: Is it better to use a treatment that might have some benefit but definitely has some risk or not to use a treatment that has any risk unless there is proven benefit?