Elevated plasma low‐density lipoprotein‐cholesterol (LDL‐C) concentration is the most important risk factor for atherosclerotic cardiovascular diseases (CVDs). Proprotein convertase subtilisin/kexin type 9 (PCSK9) is a ubiquitously expressed serine proteinase which plays a key role in cholesterol metabolism, but has been found to be implicated in some other lipid‐independent physiological processes. In this review, the role of PCSK9 was evaluated not only concerning lipid metabolism but also hepatitis C virus (HCV) infection, bacterial infections/sepsis, and septic shock. Collected data from clinical trials revealed that treatment with PCSK9 inhibitors has beneficial effects in lowering LDL‐C via inhibition of LDL‐receptors (LDL‐R), an antiviral effect on HCV infection via down‐regulating the surface expression of LDL‐R and CD81 on hepatic cells, and a positive association with increased inflammatory responses, as well as with septic shock by down‐regulation of hepatocyte LDL‐R. On the other hand, PCSK9 inhibition by therapeutic fully humanized antibodies has positive effects in reducing elevated LDL‐C. However, their safety and tolerability is an important issue which has to be taken into consideration. In this review, the role of PCSK9 was evaluated not only concerning lipid metabolism but also hepatitis C virus (HCV) infection, bacterial infections/sepsis, and septic shock.