It is well established that smoking is the primary preventable cause of disease and death in the United States and that it is responsible for a wide range of negative health consequences, including but not limited to respiratory disease. According to the US Public Health Service, all patients attempting to quit smoking should be encouraged to use one or more effective pharmacotherapy agents for cessation except in the presence of special circumstances or in populations for which there is insufficient evidence of effectiveness (pregnant women, smokeless tobacco users, light smokers and adolescents). These medications are most effective when coupled with behavioral counseling interventions. This review article provides an overview of comprehensive (the 5 A's framework: Ask, Advise, Assess, Assist, Arrange) and brief (Ask, Advise, Refer) interventions for assisting patients with quitting, and a more detailed review of the seven first-line pharmacological agents for smoking cessation (nicotine replacement therapy formulations, bupropion SR and varenicline) and combination therapy regimens. This information will facilitate respiratory therapists in addressing the most important risk factor for pulmonary disease in the patient population that they serve.