Bloodstream infections (BSI) are a major cause of mortality, morbidity and medical cost. Even though monitoring activities have been on-going for decades, it is difficult to depict a full picture of the burden of BSI. The main reasons for shortcomings include varying study aims, definitions and inclusion criteria for both microorganisms and patients. Incidence studies are commonly hampered by difficulties in delineating the population at risk. The objective of this review was to provide a framework for comprehensive BSI monitoring systems in the future. We highlight the importance of standardized definitions and acquisition of data combined with cautious statistical analyses. Hereby, valid data on BSI can be provided for clinicians and decision makers and ultimately contribute to improvement of the quality of care for BSI patients.