We are living in the midst of the worst drug epidemic in American history, with no end in sight. How did it come to be, and what can we do about it? Couple that with alcohol abuse, which causes nearly double the number of fatal car crashes in rural areas, and you have a problem that is truly unprecedented. Rural residents have higher rates of substance abuse but are less likely to utilize treatment options. Many non-violent drug- and alcohol-related arrests lead to incarceration, which often provides little or no rehabilitation. Our prisons are filled to bursting and recidivism rates are high. This chapter surveys several of the most popular drugs in the epidemic and some government interventions, treatment methods, and case studies.