Reduction in low-density lipoprotein cholesterol (LDL-C), mainly with statins, 
has decreased the risk of cardiovascular events over the last few decades. 
However, there are several patient populations that warrant further decrease in 
LDL-C by additional cholesterol-lowering therapy other than statins. Proprotein 
convertase subtilisin/kexin type 9 (PCSK9) inhibitors are a new class of drugs 
that have been shown to further decrease LDL-C by 50-70% when administered as a 
monotherapy or on a background therapy with statins. Proprotein convertase 
subtilisin/kexin type 9 inhibitors are also an excellent example of drug 
development in which discovery of gene mutations and its clinical effects have 
rapidly progressed into successful preclinical and clinical studies with 
multiple Phases 1-3 clinical trials completed or ongoing to date. This review 
summarizes the rapid evolution of the drug from genetic discovery to 
identification of targets for the drugs, to animal and human testing, and to 
large clinical outcomes trials, followed by discussion on foreseeable challenges 
of PCSK9 inhibitors.