The increasing prevalence of obesity in developed nations has far-reaching implications for medical toxicology. The management of obese patients is complicated by comorbid illnesses, changes in cardiovascular and respiratory physiology, alterations in pharmacokinetics, and a lack of studies to identify appropriate dosing for current therapeutics and antidotes. In this review article, we examine obesity-associated physiologic and pharmacokinetic changes that may increase the vulnerability of obese patients to overdose. Further research is needed to characterize the relationship between drug toxicity and obesity.