The safety of medication use in primary care is an area of increasing concern for health systems internationally. Systematic reviews estimate that 3-4% of all unplanned hospital admissions are due to preventable drug-related morbidity, the majority of which have been attributed to shortcomings in the prescribing and monitoring stages of the medication use process. We define high-risk prescribing as medication prescription by professionals, for which there is evidence of significant risk of harm to patients, and which should therefore either be avoided or (if avoidance is not possible) closely monitored and regularly reviewed for continued appropriateness. Although prevalence estimates vary depending on the instrument used, cross-sectional studies conducted in primary care equivocally show that it is common and there is evidence that it can be reduced. Quality improvement strategies, such as clinical decision support, performance feedback and pharmacist-led interventions have been shown to be effective in reducing prescribing outcomes but evidence of improved patient outcomes remains limited. The increasing implementation of electronic medical records in primary care offer new opportunities to combine different strategies to improve medication safety in primary care and to integrate services provided by different stakeholders. In this review article, we describe the spectrum of high-risk medication use in primary care, review approaches to its measurement and summarize research into its prevalence. Based on previously developed interventions to change professional practice, we propose a systematic approach to improve the safety of medication use in primary care and highlight areas for future research.