The associative storage of information, in addition to subject categorization, provides a powerful means of recalling a significant amount of related information with little input. The subcortical limbic system devotes a good deal of processing power and anatomy to correctly associate information, both for species and self-survival, using reward-driven learning via the projections of dopaminergic midbrain neurons and the hippocampus. These two systems are continuously and largely subconsciously updating this information based on experience, so that animals don't have to be overly occupied about predictable events. As humans, like other animals, it is advantageous that our brains care more about the unexpected. The drug nicotine, when consumed in its many forms, is constantly paired with a variety of sensory and environmental cues, and this associated information is stored using operant and classical conditioning mechanisms for future retrieval. These nicotine-induced associations are obviously not advantageous for survival. However, because addictive drugs greatly activate the reward pathway, they are repeated and any associatively-stored contextual information becomes a strong secondary predictor of drug expectation, perhaps inducing motivationally driven-states that facilitate drug-seeking behavior, and trigger the craving and withdrawal which ultimately may be responsible for the chronic relapsive nature of this disease. Initially, the brain seems to be able to adapt homeostatically to the presence of the drug, such that it can function normally with the drug on board. However, when the drug is absent, perhaps during cessation attempts, activating anti-reward systems, notably stress, may induce further brain changes, such that the nicotine-affected brain can never return to its naïve state even following a prolonged absence from the drug. During the abstinent period, secondary associative contexts or sensory cues may become the major trigger for a lifetime of an induced predisposition to nicotine by providing the drive for eventual nicotine relapse and abuse. In this review, I will discuss what is known about changes, induced by chronic nicotine use, in the hippocampus on the cellular and circuit levels. Furthermore, I attempt to link these changes to the rest of the reward system with the goal of ultimately working towards a model of how exposure to a small amount of nicotine can lead to the addictive behavior that affects 1 in 5 of the world's population - over 1 billion people. Specifically, the functional role of the hippocampus, traditionally associated with the relapse stage of addiction, will be re-analyzed in the broader context of the entire addiction process, much of which will involve assembling data that has been viewed largely in isolation, and will, by necessity, involve a certain amount of speculation. © 2012 by Nova Science Publishers, Inc. All rights reserved.