The peroxisome proliferator-activated receptor γ (PPARγ) coactivator-1s (PGC-1s) can induce the expression of several downstream genes that play pivotal roles in the regulation of mitochondrial biogenesis and metabolism in the heart. Moreover, PGC-1 signaling pathways have also been reported to play a critical role in cardioprotection. Given the significance of PGC-1 coactivators, we summarize the current literature on the molecular mechanisms and roles of PGC-1s in cardiac metabolism. Thus, in this review, we first introduce the basic knowledge regarding PGC-1 signaling pathways. We then discuss their roles in heart metabolism. Moreover, we describe several significant treatments that target the PGC-1 signaling pathway. This review presents the significant roles of PGC-1s in cardiac metabolism and may contribute to the promotion of PGC-1 signaling pathway as a novel therapeutic target.