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In early April 2018, Dr. Maria Oquendo, President of the American Psychiatric Association, and Dr. Nora Volkow, Director of the National Institute on Drug Abuse, published a thought-provoking article in the New England Journal of Medicine about the role of suicide in the opioid overdose epidemic, referring to the relationship between them as a “hidden tragedy.” Drs. Oquendo and Volkow drew our attention to the twinning of the opioid (and other drug) overdose and suicide epidemics, but these are not the first or only drug-related “twin epidemics.” Numerous other related conditions, including pain disorders, adverse childhood experiences, posttraumatic stress disorders, HIV/AIDS, polydrug use and toxicity, and certain social determinants of health, may interact in a multiplicative and/or cumulative manner to adversely impact individuals and populations.Syndemic theory (Singer, 2009; Singer, Bulled, Ostrach, & Mendenhall, 2017) can be helpful for describing how certain conditions cluster and interact synergistically to exacerbate health effects, problem severity, and disease progression. This column argues that the opioid crisis can accurately be considered not only a singular epidemic, or even a singular syndemic when twinned with a suicide epidemic, but also a complex phenomenon that consists of multiple, related syndemic conditions in addition to suicide. These are multidimensional disorders, with multiple, often overlapping etiologies, so single-minded approaches will be ineffective. Consideration of syndemic interactions and their cumulative and multiplicative effects are helpful for guiding treatment and prognosis for individuals, and program planning and health policy for population health (Singer et al., 2017).