Lipid rescue is used as treatment of various poisonings despite weak scientific evidence. Some experimental studies have indicated a positive effect, but others have not. Clinical studies are lacking, wherefore a systematic review of virtually all published human case reports is presented. The case reports were searched for in PubMed and Web of Science and examined by two experts according to an assessment form grading the probability for a causal connection between lipid rescue and improved symptoms. A total of 160 cases were finally included, of which 30 had no positive effect of lipid rescue. Among the 130 included cases with alleged positive effect, 94 were oral poisonings and 36 were cases with local anesthetic systemic toxicity (LAST). The experts’ assessment resulted in a “certain” causal connection in three cases with LAST but not in oral poisoning. Moreover, the mean assessment score among the oral poisonings was significantly worse than the corresponding score in the cases with LAST. The average log p-value of the main toxins among the oral poisonings was significantly lower than the corresponding p-value in the cases with LAST. Among the oral poisonings, 91% had received some other resuscitative treatment more or less simultaneously with lipid rescue. Considering the findings of this study and the increasingly reported adverse effects of lipid rescue, it’s reasonable to strictly limit its use in clinical practice. We would not recommend it in oral poisonings.