Peroxisome proliferator activated receptors (PPARs) are ligand-activated transcription factors and members of the nuclear hormone receptor superfamily. PPARβ/δ is ubiquitously expressed and has a central role in homeostasis, and has been suggested as a therapeutic target for a number of metabolic and cardiovascular disorders. This important nuclear receptor controls transcription under different modes of molecular activity which directly control the cellular function and fate of tissues. This complex activity of induction and transrepression of gene expression (with and without exogenous ligands) is poorly understood and yet understanding this molecular control through novel drug development would led to control over a key molecular switch in all cells. This review outlines the main molecular mechanisms of PPARβ/δ, and links the modes of activity to the signalling pathways in inflammation, proliferation and senescence, with the goal to understand how this will translate into novel drug design to control the PPARβ/δ molecular switch.