Vaccenic acid (VA) (t11 octadecenoic acid) is a positional and geometric isomer of oleic acid (c9-octadecenoic acid), and is the predominant trans monoene in ruminant fats (50%–80% of total trans content). Dietary VA can be desaturated to cis-9,trans-11 conjugated linoleic acid (c9,t11-CLA) in ruminants, rodents, and humans. Hydrogenated plant oils are another source of VA in the diet, and it has been recently estimated that this source may contribute to about 13%–17% of total VA intake. In contrast to suggestions from the epidemiological studies, the majority of studies using cancer cell lines (Awad et al. 1995; Miller et al. 2003) or rodent tumors (Banni et al. 2001; Corl et al. 2003; Ip et al. 1999; Sauer et al. 2004) have demonstrated that VA reduces cell growth and (or) tumor metabolism. Animal and in vitro studies suggest that the anti-cancer properties of VA are due, in part, to the in vivo conversion of VA to c9,t11-CLA. However, several additional mechanisms for the anti-cancer effects of VA have been proposed, including changes in phosphatidylinositol hydrolysis, reduced proliferation, increased apoptosis, and inhibition of fatty acid uptake. In conclusion, although the epidemiological evidence of VA intake and cancer risk suggests a positive relationship, this is not supported by the few animal studies that have been performed. The majority of the studies suggest that any health benefit of VA may be conferred by in vivo mammalian conversion of VA to c9,t11-CLA. VA acts as a partial agonist to both peroxisome proliferator-activated receptors (PPAR)-α and PPAR-γ in vitro, with similar affinity compared to commonly known PPAR agonists. Hypolipidemic and antihypertrophic bioactivity of VA is potentially mediated via PPAR-/-dependent pathways.