In the early 1930s, commercially marketed remedies promising weight loss began to appear more frequently in pharmacies and through mail-order catalogs. On May 21, 1933, physicians and public-health officials documented a cluster of fatal cases in which patients who had taken an appetite-suppressant preparation suffered severe adverse effects and died. These incidents are among the earliest clearly recorded instances in which use of a diet drug was causally associated with deaths, and they helped shape subsequent medical and regulatory scrutiny of slimming compounds. The preparations promoted at that time varied widely in ingredients and quality. Some products contained stimulants such as amphetamine derivatives or other sympathomimetic agents; others included toxic substances or improperly formulated chemical mixtures. Medical understanding of pharmacology, dosing, and long-term safety for such agents was limited, and oversight of over-the-counter and patent medicines was still evolving after the passage of early food-and-drug legislation in the United States and parallel measures elsewhere. Reports from 1933 described severe cardiovascular and neurological symptoms in affected patients, consistent with overdoses or toxic reactions to potent stimulants and other active ingredients used to suppress appetite. Physicians who investigated noted that some victims had taken multiple doses or combined the slimming preparation with other medications, heightening risk. Pathological examinations in certain cases identified heart damage and other organ pathology consistent with drug-induced injury. Public reaction to the fatalities contributed to growing calls for stricter controls on medicinal claims and the labeling of proprietary remedies. Although systematic clinical trials and the regulatory frameworks familiar today were not yet standard, these early deaths underscored the potential for serious harm from untested weight-loss agents and influenced later public-health responses, including tighter advertising restrictions and demands for clearer ingredient disclosure. Historians and medical researchers point to the 1930s as a formative period for modern drug regulation: adverse events such as the May 21, 1933 deaths helped fuel debates among physicians, legislators and consumer advocates about how to protect the public from hazardous pharmaceuticals marketed with unsubstantiated claims. Precise details about the specific commercial product(s) involved, including exact formulations and manufacturers, can be sparse or variably reported in contemporary accounts; recordkeeping and investigative methods then were not as rigorous as they are now. The legacy of these early cases is twofold. Clinically, they illustrate how potent pharmacological effects—especially from stimulants and poorly controlled preparations—can lead to fatal outcomes when used without adequate dosing guidance or safety data. Institutionally, the incidents contributed to the incremental development of regulatory practices requiring greater evidence of safety and clearer labeling for drugs, which would expand substantially in later decades. While modern diet drugs undergo extensive testing and regulation, the 1933 fatalities remain a historical reminder of why safety evaluation, transparent ingredients, and medical oversight are essential when medications that affect the cardiovascular or nervous systems are used for non-life-threatening indications like weight loss.