Chronic heart failure (HF) remains a major medical problem in the developed world, with rapidly rising prevalence, substantial morbidity, and high costs. The concept of titrating chronic HF therapies using physiologic markers, so called "biomarker guided therapy (BGT)", has become an area of substantial interest in HF given the underutilization of evidence-based medications and suboptimal outcomes with current management strategies. Several recent trials of BGT have had mixed results, with some demonstrating improved outcomes and others showing no benefit. The heterogeneity of patient populations compounded by the lack of standardized BGT algorithms and trial endpoints has complicated interpretation of these results. This article reviews the rationale, accumulated data, and unanswered questions for BGT in chronic HF.