More than 300 forms of mitochondrial disease and dysfunction have been identified, and it is estimated that 1 in 4,000 people are afflicted. Regardless of classification, all mitochondrial disorders lead to reduced energy production, increased oxidative stress, and damaged mitochondria. Since mitochondria are responsible for producing virtually all energy needed by the body, those organs and systems which have high energy demands, such as the liver, kidneys, pancreas, brain, digestive tract, and muscles, are impacted the most by mitochondrial disease and dysfunction. Eventually, the continuing cycle of low energy production and high oxidative stress leads to cell death and disease progression. At the present time, there are no cures for these disorders. The best approach to treatment is to make lifestyle and dietary changes aimed at improving energy production and antioxidant action. Studies have shown that engaging in regular exercise and consuming certain phytochemicals can increase the number and content of mitochondria in a cell. Studies have also shown that consuming certain vitamins, minerals, and bioactive compounds can increase cellular respiration and ATP production. Since energy (ATP) is produced in the mitochondria, ATP production can be improved by increasing the mitochondrial content of a cell (mitochondrial biogenesis) or by improving the redox reactions involved in its cellular respiration. It has been long established that aerobic endurance exercise, such as biking and walking, leads to mitochondrial biogenesis. With regards to high-intensity interval training (HIIT) and strength/resistance training (RT), researchers found that those engaging in HIIT had significant improvement in the functioning of ribosomes, the organelle responsible for producing the cells’ building blocks of proteins. This led to a robust increase in mitochondrial protein synthesis and enhanced mitochondrial function. In addition, researchers discovered that chronic resistance exercise training significantly increased both mitochondrial respiratory capacity and ATP-producing capacity of skeletal muscle. While most people are familiar with conditions such as Parkinson’s disease, Alzheimer’s disease, ALS, and muscular dystrophy, it is not well known or understood that (1) such conditions are the result of mitochondrial dysfunction, and (2) it is this dysfunction that drives the progression of the disease. Essentially, the mitochondria in virtually every one of the 37 trillion cells in the body produce less energy than needed and more free radicals than the mitochondrial defense system can neutralize. The excess free radicals cause oxidative damage to the mitochondrial DNA, membranes, and defense systems, leading to further mitochondrial dysfunction and oxidative damage. Eventually, the reduced energy production and increased oxidative damage leads to cell death and the progression of the disease. Until a cure is found, steps should be taken to improve ATP production through increased mitochondrial content or function. First, make lifestyle changes, such as engaging in regular aerobic and weight/resistance exercise, avoiding mitotoxic prescription and over-the-counter drugs, and avoiding environmental pollutants, such as pesticides, smoke, mycotoxins, heavy metals, and phthalates. Second, make dietary changes so that the foods eaten and supplements taken provide the vitamins, minerals, and bioactive substances needed to support cellular respiration and antioxidant defense. While it is never too late to make these changes, it is also never too early. Some researchers have suggested that babies should be tested at birth for certain genetically-linked mitochondrial conditions so that dietary protocols aimed at preserving mitochondrial function can be implemented as soon as possible. The best defense is a strong offense.