Background: Quetiapine is an antipsychotic, widely prescribed off-label by family physicians, despite evidence that safer alternatives exist. The aim of this research was to explore, in-depth, family physicians’ reasons for this behavior. Methods: Qualitative interviews with fifteen urban family physicians in Alberta, Canada. Participants were purposively selected based on gender, years of experience, and practice type. Interviews explored participants’ experiences prescribing quetiapine. Interviews were recorded, transcribed verbatim, and coded using thematic analysis. Results: A wish to support complex patients’ day-to-day function without causing benzodiazepine addiction motivated participants to prescribe quetiapine. The indications were varied and included incomplete symptom resolution, unclear or multiple mental health diagnoses, and complicated psychosocial problems. Family physicians benchmarked their prescribing against peers and were reluctant to stop medication started by colleagues. Limited knowledge of quetiapine’s side effects led prescribers to choose low doses. Interpretation: Quetiapine helped family physicians treat patients with complex mental health problems without prescribing benzodiazepines, but awareness of adverse effects of quetiapine was poor. Education about quetiapine should combine psychopharmacology with multi-disciplinary educational initiatives, which focus on symptom resolution, co-morbidity and non-drug options to promote more appropriate prescribing.