OBJECTIVES: Chronic heart failure (CHF) is a major health issue because of its growing prevalence, morbimortality and associated resource consumption. Beta blockers have been shown to be effective and cost-effective therapies for CHF. The aim is determining what beta blocker constitutes the most efficient therapy for CHF patients in Spain. METHODS: Systematic review of primary (clinical trials) and secondary (meta-analyses, clinical practice guidelines, economic assessments and reports from independent local agencies) evidence on beta blockers for CHF issued before April 2009. Once that efficacy of each beta blocker was established, local drug databases were accessed in order to estimate the updated annual cost of each therapy and daily dose in Spain.  RESULTS: Given their similar efficacy [death RR: bisoprolol: 0.66, p<0.0001; metoprolol: 0.66, p<0.0001; carvedilol: 0.65, p<0.005, nebivolol: 0.88, p=0.21] and safety profiles, international clinical guidelines on Cardiology recommend bisoprolol, metoprolol, carvedilol and nebivolol as first choice therapies for CHF (class I and level of evidence A). Significant annual drug cost differences for bisoprolol have been previously reported by independent Spanish agency GENESIS and are confirmed with 2009 prices [bisoprolol: €22.36-114.58; metoprolol: €30.20-241.63; carvedilol: €39.24-264.62; nebivolol: €52.50-420.01]. When hospitalization costs are included, a recent meta-analysis of beta blockers for CHF in Spain proved that bisoprolol is not only the cheapest beta blocker therapy but even a more efficient alternative than placebo [2005 prices: bisoprolol: €414.28; metoprolol: €507.64; carvedilol: €888.50; placebo: €484.96]. Budget impact analysis yields that bisoprolol implies a saving of 26-53% of metoprolol cost of therapy per year and patient, 43-57% when compared to carvedilol and 57-73% versus nebivolol.   CONCLUSIONS: According to recently updated Cardiology guidelines and evidence issued by independent bodies, bisoprolol gathers pharmacologic, legal and pharmacoeconomic characteristics that confirm their being the most efficient beta blocker (both in terms of cost-benefit and cost-effectiveness) for CHF patients in Spain.