Abstract Peroxisome proliferator-activated receptors (PPARα, β/δ, and γ), members of the nuclear receptor transcription factor superfamily, play important roles in the regulation of metabolism, inflammation, and cell differentiation. All three PPAR subtypes are expressed in the cardiovascular system with various expression patterns. Among the three PPAR subtypes, PPARδ is the least studied but has arisen as a potential therapeutic target for cardiovascular and many other diseases. It is known that PPARδ is ubiquitously expressed and abundantly expressed in cardiomyocytes. Accumulated evidence illustrates the role of PPARδ in regulating cardiovascular function and determining pathological progression. In this chapter, we will discuss the current knowledge in the role of PPARδ in the cardiovascular system, the mechanistic insights, and the potential therapeutic utilization for treating cardiovascular disease.