Introduction <p>Vulnerability to heat-related illnesses may be increased by certain drugs due to various mechanisms. Whereas in articles only rough classifications of heat-vulnerability increasing drugs (HVID) are mentioned, a detailed compilation of suspected HVID is still missing. Aim of the study was to identify HVID.</p> Methods <p>Using data from the literature, potential HVID were searched. The evidence for increasing heat-vulnerability, based on PubMed research, was rated as „high“, „possible“ or „unlikely“ by 3 investigators, independently and blinded to the others’ results.</p> Results <p>The initial search retrieved 572 potential HVID. After analyzing 27 trials in healthy subjects, 25 cohort-studies, 19 case-reports, 14 reviews, 7 prospective trials in patients and 4 pharmacovigilance-studies, the evidence to increase heat-vulnerability was assessed as “high” for 110, “possible” for 390 and “unlikely” for 72 drugs. Drugs for the nervous-system, cardiovascular-system and alimentary-tract were most frequent. Hypohidrosis (<i>n</i> = 127), disturbed thermoregulation (<i>n</i> = 35) or skin-circulation (<i>n</i> = 15) and dehydration (<i>n</i> = 10) were frequent mechanisms. Outcome events in cohort-studies were heat-illness/dehydration (<i>n</i> = 10), causes of death (<i>n</i> = 5), heat-related hospital admissions (<i>n</i> = 4), heat-stroke (<i>n</i> = 4), drug-overdose in heat-periods (<i>n</i> = 1) and hypohidrosis (<i>n</i> = 1). Comedication, when reported, disclosed additional HVID in all patients. Conflicting results about heat-vulnerability properties were found for 10 HVID.</p> Conclusion <p>Knowledge about HVID and their clinical relevance is limited. The quality of data is poor and derives mainly from young and healthy subjects. The outcome events are heterogeneous. Interdisciplinary research involving pharmacologists, physicians of different disciplines, pharmacists and health-care workers is needed to create and evaluate plans about modification of drug-therapy during heatwaves.</p>