Given the widespread incidence of smoking as well as its deleterious health effects, it is crucial to examine practical and cost effective prognostic markers assessing its health impact. Heart rate variability (HRV) is a straightforward and cost effective technique to foresee health problems of cardiovascular nature and may be used to predict in advance smoking-induced health effects. In this review we evaluate the existing biological evidence regarding the effects of smoking on HRV and their associated cardiovascular consequences. In addition, we summarize fundamental information on the various HRV indicators and their diagnostic significance in relation to heart failure. An in depth analysis of the various HRV indices characterizing changes in the activation of the autonomic nervous system is provided together with a critical evaluation of all evidence published to date on the influence of chronic and acute active and passive smoking on HRV. Overall, the vast majority of published evidence suggests that acute and chronic active and passive smoking generate marked disruptions in the normal autonomic nervous system functioning characterized by increased sympathetic drive and reduced HRV and parasympathetic modulation. The proposed mechanisms that may generate this smoke-induced HRV reduction as well as its clinical implications are thoroughly evaluated.