Cardiometabolic syndrome is a mixture of interrelated risk factors predisposing individuals to elevated risk of
atherosclerotic cardiovascular disease and type 2 diabetes mellitus. Nuclear receptors, specifically peroxisome
proliferator-activated receptors (PPARs), were identified to play a pivotal role in the regulation of metabolic homeostasis.
However, with rosiglitazone currently under intense scrutiny great concerns have arisen regarding the safety of the
thiazolidinedione PPAR-γ agonist family as a whole. This review discusses the current concern with PPAR-γ agonists by
exploring if PPARs can still be considered worth pursuing as a viable target for cardiovascular diseases. We examine
current research focusing on identifying ligands that are dual and pan-PPAR agonists, selective PPAR-γ modulators,
PPAR-β/δ agonists and that are of natural origin.