Tachycardia is an independent risk factor for mortality and morbidity in different clinical conditions such as coronary artery disease, myocardial infarction, as well as congestive heart failure. Evidence suggests that an elevated heart rate is associated to increased mortality even in septic shock. It has been recently demonstrated that tachycardia persisting at 24 hours, after volume resuscitation and commencement of vasopressors, early identifies a particularly severe subset of septic shock patients. These high-risk patients would likely benefit most from HR control. A reduction in HR should be therefore considered as one of the therapeutic targets to improve patient outcome. Nevertheless, reducing HR in septic shock is difficult, because the right time for treatment and the optimal HR range are not currently defined. Based on the underlying mechanisms of elevated heart rate in septic shock, both beta blocker esmolol and hyperpolarization-activated cyclic nucleotide gated channel inhibitor ivabradine appear to be the most appropriate drugs for treating elevated HR. Nevertheless, the effectiveness and safety of these agents, the degree of HR reduction, as well as the appropriate target population, should be better defined before widely adopting this therapeutic strategy in the common clinical practice. The aim of this chapter is therefore to provide an overview of the underlying mechanisms of sepsis-induced tachycardia and their implications in the clinical management of affected patients.