Background: Bloodstream infection (BSI) is a major public health concern due to its severity-related consequences. These infections pose a human health risk, as they can result in human morbidity and mortality over a short period of time. Blood culture remains the gold standard and major tool for the diagnosis of BSI. Blood culture sampling is commonly indicated before administering antimicrobial therapy, whereas the daily therapeutic adjustment to the antibiogram is an effective intervention in management of BSIs. Compliance with the microbiological criteria-based protocols for pathogen identification and antimicrobial susceptibility testing allow treatment correction within 48-72 hours. Interpretation of positive blood cultures may sometimes present a dilemma for clinicians and microbiologists and, therefore, the test findings should be evaluated in the context of the clinical picture. Conclusions: Over the last decades, we have witnessed an outbreak in the number of BSI studies. The implementation of a standardized algorithm on criteria of a complete blood count sampling, processing and interpretation of the results will help increase the yield rate of BSI pathogens and ultimately improve care management of the patients with BSI. The education and training of medical staff, engaged in BSI patient care is vital in developing good practice, preventing blood culture contamination and obtaining fast and accurate outcomes.