This chapter starts out with a theoretical discussion of the meaning of “drug”. As it turns out, three different kinds of psychoactive drugs can be distinguished. Central to this distinction is the understanding of appropriate medical use, which is subject to change. Historical examples illustrate how our personal and also governments’ ways to think about drugs changed since the nineteenth century. In the past, colonial authorities were the biggest drug traders and countries even waged war to enforce open markets. Cocaine, opium, and nitrous oxide (laughing gas) are addressed in detail. The legal regulation of that last substance even changed as the book was being written. The framework for people’s instrumental substance use is then introduced. It distinguishes different reasons for which drugs can be instrumentalized. Several common substances are described subsequently, addressing their respective risks and benefits. The final section presents important values that can guide moral decisions about drug use.