Drug addiction is a chronic brain disease with a high incidence of relapse. Environmental cues that previously and repeatedly associated with drugs of abuse easily evoke relapse to addicts even after long period of drug-free state. Such a long lasting property of conditioning is considered a form of long-term memory and has a strong correlation with synaptic plasticity like long-term potentiation (LTP). Protein kinase M zeta (PKMzeta) has been known to play an important role in the maintenance of long-term memory as well as LTP in various brain areas. Likewise, in a few brain areas examined out of the rewarding circuit, PKMzeta seems to play a similarly important role in the maintenance of conditioned memory. These results suggest that PKMzeta may become a new target to manipulate to reverse pre-formed drug-related memory and accompanied behaviors.