The duration of each cardiac cycle is measured on an ECG as the distance between the peaks of consecutive R waves (RR interval), with the inverse value corresponding to the heart rate (HR) changing in a beat-to-beat manner. HR accelerations are reflected as shortenings of the RR intervals, HR decelerations as the lengthening of RR intervals. HR asymmetry is a physiological phenomenon caused by an unequal input of HR decelerations and accelerations to the HR variability. Naturally occurring consecutive values of RR intervals create a time series composed of acceleration and deceleration runs of differing lengths. For example, a single HR acceleration, a pair of HR decelerations, a run consisting of five consecutive HR decelerations or a run composed of eight accelerations in a row. These runs make up the so-called heart rate microstructure that has asymmetric properties due to the unequal contribution of acceleration and deceleration runs. The asymmetry of the HR microstructure is physiological in healthy individuals, however, the asymmetric properties can be significantly altered in some clinical conditions, such as myocardial infarction, obstructive sleep apnoea, chronic obturatory pulmonary disease or sepsis in infants. An abnormal HR microstructure has predictive value in survivors of myocardial infarction or patients with clinical indications for exercise treadmill stress test, e.g., for total mortality. In this review, we present and explain how the asymmetric properties of HR microstructure can be quantified, summarising the available data regarding the clinical and predictive value of this phenomenon and its analysis.