The major dietary sources of trans fatty acids (TFAs) in most countries are partially hydrogenated vegetable oils. TFA consumption is a modifiable dietary risk factor for metabolic syndrome, diabetes mellitus, and coronary heart disease. Here, we review the available data on various effects of TFAs, including metabolic and signaling pathways that mediate these effects, affected tissues, and relationships with clinical end points. TFA consumption causes metabolic dysfunction: it adversely affects circulating lipid levels, triggers systemic inflammation, induces endothelial dysfunction, and, according to some studies, increases visceral adiposity, body weight, and insulin resistance. Dietary TFAs influence the function of multiple cell types, including hepatocytes, adipocytes, macrophages and endothelial cells. Among dietary fats and nutrients, TFAs seem to have a unique cardiometabolic imprint that is linked to insulin-resistance and metabolic-syndrome pathways. Consistent with these adverse physiological effects, consumption of even small amounts of TFAs (2% of total energy intake) is consistently associated with a markedly increased incidence of coronary heart disease. Relationships between TFA consumption and diabetes mellitus have been less consistent, possibly owing to differences in study designs. Nevertheless, the documented adverse effects of TFAs underscore their potential to cause harm and the importance of policy measures to minimize consumption of industrially produced TFAs.