Heart failure is the final stage of cardiovascular disease development, and heart failure treatment strategies need to be explored. Cyclic adenosine monophosphate ( cAMP) and cyclic guanosine monophosphate ( cGMP) are second messengers that regulate signal transduction, which are hydrolyzed by a group of distributed and functional specific phosphodiesterases (PDEs) in cardiomyocytes, which play key roles in the pathogenesis of normal cell activity and heart failure. The efficacy of PDE3 and PDE5 inhibitors has been clinically recognized, and clinical and basic researches are constantly updating for their mechanisms of action. Here we summarize these research advances, which in turn helps us to understand the strategies and research directions of heart failure treatment