The tobacco plant produces numerous biologically active substances, including various alkaloids that are particularly significant for health. From a global perspective, the smoking of commercial cigarettes, pipe and cigar products, shisha smoking, oral snuff, and chewing tobacco continues to impact large segments of the population, posing a substantial health issue. Additionally, alternative tobacco products or nicotine-containing products must be considered alongside traditional tobacco products, particularly heated tobacco products, electronic cigarettes (including electronic nicotine and non-nicotine delivery systems), and nicotine pouches. While the severe health effects of tobacco-containing products—including respiratory and cardiovascular issues, as well as cancers affecting multiple organs—have been recognized for decades, the health impacts of alternative smoking and vaping products and techniques remain less studied. Nonetheless, there is a growing body of evidence regarding the health effects of these alternatives. Therefore, this document provides a brief overview of the chemical-physical characteristics and usage patterns of various tobacco- and smoking-related substances, highlighting their primary health risks and toxicokinetic properties, along with references to additional scientific literature. The primary objective is to present detailed information about their occurrence in human matrices, such as blood, urine, and breast milk. For context, the information covers tobacco smoking, shisha usage (water pipes), e-cigarettes, smokeless tobacco or nicotine products, and cannabis use.