The heart is one of the most fascinating organs in living beings. It beats up to 100,000 times a day throughout the lifespan, without resting. The heart undergoes profound anatomical, biochemical, and functional changes during life, from hypoxemic fetal stages to a completely differentiated four-chambered cardiac muscle. In the middle, many biological events occur after and intersect with each other to regulate development, organ size, and, in some cases, regeneration. Several studies have defined the essential roles of the Hippo pathway in heart physiology through the regulation of apoptosis, autophagy, cell proliferation, and differentiation. This molecular route is composed of multiple components, some of which were recently discovered, and is highly interconnected with multiple known prosurvival pathways. The Hippo cascade is evolutionarily conserved among species, and in addition to its regulatory roles, it is involved in disease by drastically changing the heart phenotype and its function when its components are mutated, absent, or constitutively activated. In this review, we report some insights into the regulation of cardiac physiology and pathology by the Hippo pathway.