Laboratory animals self-administer most, though not all, drugs of abuse. Recent evidence shows that with increased drug availability, most laboratory rats develop all the major behavioral signs of addiction, including: 1) drug intake escalation, 2) increased motivation for the drug, 3) difficulty to abstain, 4) decreased reward function, and 5) inflexible drug use. The large prevalence of addicted rats may suggest that they are particularly vulnerable to develop compulsive drug use. I review evidence showing that this apparent vulnerability results in large part from the lack of positive (i.e., alternative non-drug rewards) and negative (i.e., costs) incentives capable of turning animals away from the pursuit of drugs. In particular, most animals seem to take drugs and eventually become addicted, not because drugs are intrinsically addictive, but more likely because drugs are the only significant sources of reward available in the laboratory. Laboratory animals would therefore represent more of a model of high-risk human groups than of the general population. Consequently, they should be more suited for searching factors that protect from, rather than predispose to, drug addiction. Reconsidering the environmental background of drug self-administration experiments in laboratory animals raises intriguing implications for understanding the initial demand for drug consumption and the transition to drug addiction, and for extrapolation from laboratory animals to humans.