In addition to the well-documented increase in deaths involving opioids over the past two decades, overdose deaths involving stimulants have also increased sharply, and recent estimates indicate a high prevalence of polysubstance abuse involving opioids and stimulants. With speakers representing a broad spectrum of expertise, including epidemiology, human behavioral pharmacology and clinical trials, pre-clinical behavioral pharmacology, and medicinal chemistry, this symposium highlights current research on opioid and stimulant co-abuse and demonstrates contributions pharmacology research can make toward addressing this rapidly growing and evolving public health challenge.