Coenzyme Q (CoQ) is an essential cofactor in oxidative phosphorylation (OXPHOS), present in mitochondria and cell membranes in reduced and oxidized forms. Acting as an energy transfer molecule, it occurs in particularly high levels in the liver, heart, and kidneys. CoQ is also an anti-inflammatory and antioxidant agent able to prevent the damage induced by free radicals and the activation of inflammatory signaling pathways. In this context, several studies have shown the possible inverse correlation between the blood levels of CoQ and some disease conditions. Interestingly, beyond cardiovascular diseases, CoQ is involved also in neuronal and muscular degenerative diseases, in migraine and in cancer; therefore, the supplementation with CoQ could represent a viable option to prevent these and in some cases might be used as an adjuvant to conventional treatments. This review is aimed to summarize the clinical applications regarding the use of CoQ in migraine, neurodegenerative diseases (including Parkinson and Alzheimer diseases), cancer, or degenerative muscle disorders (such as multiple sclerosis and chronic fatigue syndrome), analyzing its effect on patients' health and quality of life.