ABSTRACT Anticholinergic activity is pharmacologically relevant for many medicinal and natural toxins. Delirium is a common consequence of toxicity. Although a direct anti-dote, physostigmine is available, it fell out of use after case reports of suspected cardiotoxicity were propagated through the literature. Physostigmine was previously used with high frequency and to good effect to reverse anticholinergic delirium from a variety of compounds. It was also employed in cases of delirium with other, some-times unknown etiologies, without serious adverse events. At one toxicology center, physostigmine continues to be employed in the emergency department and acute hospital setting. It is given 0.02 mg/kg IV at a rate of 0.5 mg/min with repeat doses q1-2h PRN. The following reports a six-year retrospective review of the practice and a detailed prospective one-year observational study of bedside use of the antidote.