Peroxisome proliferator‐activated receptors (PPARs) are ligand‐activated transcription factors involved in several physiological processes including modulation of cellular differentiation, development, metabolism of carbohydrates, lipids, proteins, and tumorigenesis. The aim of this review is to examine how different PPAR ligands act, and discuss their use in clinical practice. PPAR ligands have a lot of effects and applications in clinical practice. Some PPAR ligands such as fibrates (PPAR‐α ligands) are currently used for the treatment of dyslipidemia, while pioglitazone and rosiglitazone (PPAR‐γ ligands) are anti‐diabetic and insulin‐sensitizing agents. Regarding new generation drugs, acting on both α/γ, β/δ, or α/δ receptors simultaneously, preliminary data on PPAR‐α/γ dual agonists revealed a positive effect on lipid profile, blood pressure, atherosclerosis, inflammation, and anti‐coagulant effects, while the overexpression of PPAR‐β/δ seems to prevent obesity and to decrease lipid storage in cardiac cells. Finally, PPAR‐α/δ dual agonist induces resolution of nonalcoholic steatohepatitis without fibrosis worsening. Peroxisome proliferator‐activated receptors (PPARs) are ligand‐activated transcription factors involved in several physiological processes. PPAR ligands have a lot of effects and applications in clinical practice. The aim of this review is to examine how different PPAR ligands act, and discuss their use in clinical practice.