Smoking tobacco cigarettes is a significant (cardiovascular) health risk factor. Although the number of tobacco cigarette users declined over the last decades, shisha smoking and e-cigarette vaping partially compensated for this health benefit. E-cigarettes may create highly addicted dual users (vaping and smoking). E-cigarettes seem not to represent a healthier alternative to tobacco smoking, although they may be less harmful. E-cigarette vaping causes oxidative stress, inflammation, endothelial dysfunction, and associated cardiovascular sequelae. This is primarily due to a significant overlap of toxic compounds in the vapor compared to tobacco smoke and, accordingly, a substantial overlap of pathomechanistic features between vaping and smoking. Whereas the main toxins in vapor are reactive aldehydes such as formaldehyde and acrolein, the toxic mixture in smoke is more complex, comprising particulate matter, reactive gases, transition metals, volatile organic compounds, and N-nitrosamines. However, it seems that both lifestyle drugs impair endothelial function to a quite similar extent, which may be due to the role of oxidative stress as the central pathomechanism to mediate endothelial dysfunction and vascular damage. Finally, the main selling argument for e-cigarette use that they help to quit smoking and get rid of nicotine addiction may be false because it seems that e-cigarettes instead trigger the opposite—younger entrance age and more frequent use. With our review, we summarize the adverse health impact of tobacco cigarettes and e-cigarettes, emphasizing the detrimental effects on endothelial function and cardiovascular health.