Cardiovascular diseases (CVD) are associated with the dysfunction of endothelium that regulates the contractile state of vascular walls and cellular composition. Recent large clinical trials indicated that lipid-modifying interventions decrease the risk of CVD in patients with hypercholesterolemia and in those with relatively normal levels of LDL cholesterol. They also highlighted lipid-independent role of well-established lipid-lowering drugs- statins- which inhibit 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase and are used in the treatment of hypercholesterolemia and reduction of atherosclerosis. Novel therapeutic approaches of statins include their influence on heme oxygenase 1 (HO-1) and HO-1 related signaling pathways such as activator protein (AP)-1, protein kinase G (PKG), extracellular matrix-regulated kinase (ERK), p38 MAPK or NFκB in vascular wall cells. This review aimed to describe the molecular mechanisms involved in the induction of HO-1 under different statins in the most common CVD.