Cigarette smoking is becoming more prevalent in developing countries, such as China, and is the largest single cause of preventable death worldwide. New emerging reports are highlighting how chronic cigarette smoking plays a role in neural dysfunctions, such as cognitive decline. Basic animal experimental studies have shown that rats undergo persistent pathological brain changes after being given chronic levels of nicotine. What is perhaps less appreciated is the fact that chronic cigarette smoking induces subtle anatomical changes in the human brain. Consequently, this chapter aims to summarize and integrate the existing magnetic resonance imaging studies on both gray- and white-matter marcostructural and microstructural changes. The reviewed studies demonstrate that chronic cigarette smoking results in discrete and localized alterations in brain region tissue (both the gray and white matter of different brain regions), which may, in part, be responsible for different neural dysfunctions. In addition, we further discuss the possible pathological and neurobiological mechanisms of these nicotinic effects on the brain tissue. We will also address the limitations of the current studies on this issue and identify opportunities for future research.