This review comprises the impact of trans fatty acids (tFA) and conjugated linoleic acids (CLA) in the human nutrition. The knowledge of the impact of the relation between dietary tFA and the risk of cardiovascular diseases diabetes mellitus type-2, and cancer increased in the last years. There is increasing evidence that the effects of tFA on human health differ among positional trans-isomers. CLA show various metabolic properties mainly anti-cancerogenic, anti-inflammatory, and antiatherogenic, with potent impact in humans.