Arterial hypertension remains one of the leading modifiable risk factors for cardiovascular morbidity and mortality worldwide. Although effective antihypertensive treatments are widely available, a considerable proportion of patients fail to achieve recommended blood pressure targets when treated with monotherapy. Both international and Greek guidelines emphasize the early initiation of combination therapy, preferably in the form of single-pill combinations (SPCs), in order to improve adherence and clinical outcomes.The objective of this study was to review the available evidence regarding the use of single-pill combinations in Greece and internationally, and to identify discrepancies between guideline recommendations and real-world clinical practice.A narrative review of the Greek and international literature was conducted using the PubMed, Scopus, and Google Scholar databases. In addition, current guidelines from the European Society of Cardiology/European Society of Hypertension (ESC/ESH) and the Hellenic Society of Hypertension were reviewed. Data on national and international SPC utilization rates, as well as factors influencing their implementation, were analyzed.In Greece, no published national or regional data are available regarding SPC utilization. Relevant prescribing data are theoretically accessible through the national e-prescription system (IDIKA), but have not been publicly released. In high-income countries, the mean SPC utilization rate is approximately 24%, with reported rates of 10.9% in Germany (2020) and a range of 10–30% across Europe. In contrast, SPC use reaches approximately 45% in low- and middle-income countries, largely due to public health policies and interventions supported by the World Health Organization. Available evidence consistently demonstrates that SPCs are associated with improved treatment adherence and higher rates of blood pressure control compared with free-drug combinations or monotherapy.Despite strong guideline recommendations, SPC adoption remains suboptimal, particularly in high-income countries such as Greece. Limited access to national prescribing data, clinical inertia, and insufficient dissemination of evidence-based combination strategies appear to contribute to this gap.A significant discrepancy exists between hypertension management guidelines and real-world SPC use in Greece and internationally. Systematic recording and public disclosure of national prescribing data, along with the promotion of evidence-based SPCs, are essential to improve blood pressure control and reduce cardiovascular risk.