Epidemiological studies have shown the association between atmospheric pollutants and increase in mortality due to cardiovascular causes, especially in patients with previous cardio-respiratory diseases. However, the pathophysiological mechanisms by which these events take place have not been elucidated. One of the proposed mechanisms by which suspended respirable particles and other pollutants produce their effect is that they modify autonomic heart control. The analysis of changes in heart rate variability (HRV) is an indicator of pollutant effect on this mechanism. The article reviews the physiologic basis of this non-invasive method, its advantages and disadvantages, and the results obtained to date through HRV analysis associated with air pollution. After reviewing the available literature, we suggest alternatives for study design, selection of risk population, exposure assessment methods, and statistical analysis methods that may be used to improve the analysis of the ambulatory ECG record to assess the cardiac risk related to exposure to air pollution.