Recent developments in noninvasive electrocardiogram (ECG) monitoring with small, wearable sensors open the opportunity to record high-quality ECG over many hours in an easy and non-burdening way. However, while their recording has been tremendously simplified, the interpretation of heart rate variability (HRV) data is a more delicate matter. The aim of this paper is to supply detailed methodological discussion and new data material in order to provide a helpful notice of HRV monitoring issues depending on recording conditions and study populations. Special consideration is given to the monitoring over long periods, across periods with different levels of activity, and in adults versus children. Specifically, the paper aims at making users aware of neglected methodological limitations and at providing substantiated recommendations for the selection of appropriate HRV variables and their interpretation. To this end, 30-h HRV data of 48 healthy adults (18–40 years) and 47 healthy toddlers (16–37 months) were analyzed in detail. Time-domain, frequency-domain, and nonlinear HRV variables were calculated after strict signal preprocessing, using six different high-frequency band definitions including frequency bands dynamically adjusted for the individual respiration rate. The major conclusion of the in-depth analyses is that for most applications that implicate long-term monitoring across varying circumstances and activity levels in healthy individuals, the time-domain variables are adequate to gain an impression of an individual’s HRV and, thus, the dynamic adaptation of an organism’s behavior in response to the ever-changing demands of daily life. The sound selection and interpretation of frequency-domain variables requires considerably more consideration of physiological and mathematical principles. For those who prefer using frequency-domain variables, the paper provides detailed guidance and recommendations for the definition of appropriate frequency bands in compliance with their specific recording conditions and study populations.