Frailty is a global health problem that impacts clinical practice. It is complex, having a physical and a cognitive component, and it is the result of many contributing factors. Frail patients have oxidative stress and elevated proinflammatory cytokines. Frailty impairs many systems and results in a reduced physiological reserve and increased vulnerability to stress. It is related to aging and to cardiovascular diseases (CVD). There are few studies on the genetic factors of frailty, but epigenetic clocks determine age and frailty. In contrast, there is genetic overlap of frailty with cardiovascular disease and its risk factors. Frailty is not yet considered a risk factor for CVD. It is accompanied by a loss and/or poor functioning of muscle mass, which depends on fiber protein content, resulting from the balance between protein breakdown and synthesis. Bone fragility is also implied, and there is a crosstalk between adipocytes, myocytes, and bone. The identification and assessment of frailty is difficult, without there being a standard instrument to identify or treat it. Measures to prevent its progression include exercises, as well as supplementing the diet with vitamin D and K, calcium, and testosterone. In conclusion, more research is needed to better understand frailty and to avoid complications in CVD.