There has been much progress recently in the area of cardiovascular mechanobiology and this Special Issue aims at taking stock. This editorial gives context of the main motivation for this special issue as well as a brief summary of its content.Cardiovascular diseases (CVD) are the primary cause of mortality, and the disease burden is projected to grow because of sedentary lifestyles and an ageing society. Vascular diseases and especially atherosclerosis, if untreated, are the dominant underlying cause of CVD. Moreover, cardiac disease progressing to heart failure is the leading cause of death among cardiovascular diseases. Underlying genetic causes and mechanisms are progressively being uncovered, e.g. through Genome-Wide Association Studies (GWAS)