Physicians (MDs), nurse practitioners (NPs), and physician assistants (PAs) in primary care (PC) specialties, as well as patients, participated in a series of peer-level focus groups to explore how colorectal cancer (CRC) screening is approached in PC. Twenty-seven focus groups were conducted, including 8 groups composed of MDs (n = 56), 7 with NP/PAs (n = 47), and 12 with patients (n = 103). Clinicians (MDs, NPs, PAs) reported discussing CRC screening during well visits and were alerted to patients in need of screening through flow sheets, chart reminders (paper, electronic) or by office personnel, and cited lack of time, patient reluctance, and challenges related to scheduling colonoscopy as barriers to screening. Clinicians identified communication skills and the convenience of office-based screening procedures as facilitators of CRC screening. Patients recalled discussing CRC screening during PC office visits and most commonly identified colonoscopy and fecal occult blood test as common CRC screening tests. Physician recommendation and knowing someone who has/had cancer were the most common factors motivating patients' decision to complete CRC screening. Results are framed according to patient and clinician perceptions of self-efficacy related to CRC screening.