Ketone bodies - 3-hydroxybutyrate (3-OHB), acetoacetate and acetone - are ancient, evolutionarily preserved, small fuel substrates, which uniquely can substitute and alternate with glucose under conditions of fuel and food deficiency. Once canonized as a noxious, toxic pathogen leading to ketoacidosis in patients with diabetes, it has by now become increasingly clear that 3-OHB possesses a large number of beneficial, life preserving effects in the fields of clinical science and medicine. 3-OHB, the most prominent ketone body, binds to specific hydroxyl-carboxylic acid receptors(HCAR) and inhibits histone deacetylase (HDAC) enzymes, free fatty acid receptors (FFAR) and the NLRP3 inflammasome, tentatively inhibiting lipolysis, inflammation, oxidative stress, cancer growth, angiogenesis, and atherosclerosis and perhaps contributing to the increased longevity associated with exercise and caloric restriction. Clinically ketone bodies/ketogenic diets have for a long period of time been used to reduce the incidence of seizures in epilepsy and may have a role in the treatment of other neurological diseases such as dementia. 3-OHB also acts to preserve muscle protein during systemic inflammation and as an important component of the metabolic defense against insulin induced hypoglycemia. Most lately, a number of studies have reported that 3-OHB dramatically increases myocardial blood flow and cardiac output in control subjects and patients with heart failure. At the moment scientific interest in ketone bodies, in particular 3-OHB is in a hectic transit and - hopefully - future, much needed, controlled clinical studies will reveal and determine to which extent the diverse biological manifestations of 3-OHB should be introduced medically.