PCSK9 inhibitors are an example of a key challenge in modern medicine: a promising new treatment that is also very costly. The storey of the discovery of PCSK9 inhibitors is one of serendipity, clever epidemiology, and rational drug development. Mutations in the PCSK9 gene were linked to low levels of low-density lipoprotein cholesterol in a sample of a French kinship (LDL-C). The low-density lipoprotein (LDL) receptor-mediated cholesterol metabolism is regulated by the proprotein convertase subtilisin/kexin type 9 (PCSK9).