We also provide insight into promising therapeutic targets for HF, focusing on the regulation of β-ARs in the heart, as well as the recent clinical studies of β3-AR agonist, AC6 gene therapy, G protein-coupled receptor kinase 2 (GRK2) inhibitors such as paroxetine and β-adrenergic receptor kinase carboxyl-terminus (β-ARKct), Ca2+/calmodulin-dependent protein kinase II (CaMKII), and sarcoplasmic/endoplasmic reticulum Ca2+-ATPase (SERCA2a) for the treatment of HF. The gene discussed is ADRB3; the disease is hydrops fetalis.