Genetic analysis in the nematode C. elegans has provided important insights into many aspects of neuronal cell biology, including functions related to addiction. Specifically, genetic and molecular screens to have been used to identify molecules involved in long-term responses to drugs of abuse and to analyze the mechanisms underlying their effects on nervous system development, plasticity, and behavior. This review presents a personal view of addiction-related research in C. elegans, and includes a discussion of technical innovations that have facilitated neurobiological analyses in C. elegans and a look at future prospects drug addiction research in simple animal models.