Millions of Americans use tobacco products despite the solidly established connection between tobacco use and disease. Approximately 440,000 people die each year in the U.S. of tobacco-related diseases. Evidence suggests that brief clinical interventions for tobacco-use, the 5 A’s, are effective and increase rates of smoking cessation. Little is known about the tobacco intervention strategies of nurse practitioners. This qualitative study explored the perceptions and practices of nurse practitioners in the delivery of brief clinical interventions for tobacco use. In addition, the study examined factors that may influence the provision of tobacco-use intervention. A written self-administered questionnaire with both closed and open-ended questions was mailed to each primary care nurse practitioner identified through the Alabama Board of Nursing database. Although the majority of nurse practitioner participants reported providing regular patient intervention for tobacco use, fewer than 15% of participants were regularly providing all five elements of the recommended 5 A’s construct. Study findings expanded the body of knowledge concerned with factors that either encouraged or were barriers to the provision of tobacco intervention. Findings also suggested a knowledge deficit related to current national guideline recommendations that may be reflective of a gap in the tobacco-related curricular content of nursing programs.