In the United States, tobacco use, mostly cigarette smoking, is the primary cause of preventable disease and death. It is commonly known that smoking raises the risk of a variety of cancers, including lung, liver, and colorectal cancers. Smokers account for 85% of lung cancer cases. Quitting smoking has been shown to lessen the risk of having a smoking-related disease among active smokers. A combination of therapy and one or more drugs is more helpful than either counseling or medication alone in helping individuals quit smoking. To provide an adequate evaluation of the different aspects of smoking cessation and the possible interventions in primary healthcare settings. We used the PubMed database for selecting articles, and the following keys were used in the mesh ( ("smoking cessation"[Mesh]) AND ("interventions"[Mesh]) OR ("primary healthcare"[Mesh])). To help smokers quit smoking, it is important to recognize that nicotine addiction is the root of their problem. Individuals with severe nicotine addiction may become mentally unstable and experience vague uneasiness. Such patients may benefit most from nicotine replacement therapy (NRT). By temporarily replacing the nicotine absorbed from smoking during smoking, the patient reduces the distressing withdrawal symptoms that occur during smoking cessation, leading to easier smoking cessation. Moreover, varenicline and sustained-release bupropion can be also used as first-line treatments for smoking cessation. In addition to pharmacological, behavioral therapies should also be provided to enhance the chances of quitting smoking.