Appropriate selection of antibiotic drugs is critical to optimize treatment of infections and limit the spread of antibiotic resistance. To better inform public health efforts to improve prescribing of antibiotic drugs, we conducted in-depth interviews with 36 primary care providers in the United States (physicians, nurse practitioners, and physician assistants) to explore knowledge, attitudes, and self-reported practices regarding antibiotic drug resistance and antibiotic drug selection for common infections. Participants were generally familiar with guideline recommendations for antibiotic drug selection for common infections, but did not always comply with them. Reasons for nonadherence included the belief that nonrecommended agents are more likely to cure an infection, concern for patient or parent satisfaction, and fear of infectious complications. Providers inconsistently defined broad- and narrow-spectrum antibiotic agents. There was widespread concern for antibiotic resistance; however, it was not commonly considered when selecting therapy. Strategies to encourage use of first-line agents are needed in addition to limiting unnecessary prescribing of antibiotic drugs.