The concept of detoxification with relevance to nutritional support is often an overlooked (and under appreciated) area in sport and exercise nutrition. Unfortunately, this term can be confused with ‘detox diets’ or fasting, involving acute and often extreme dietary approaches, and lacking in scientific validity; which this chapter is NOT about. Instead, we focus on the innate physiological processes of detoxification, which includes the associated antioxidant enzyme systems, the methylation and sulphation pathways, and others. Detoxification describes the physiological removal of exogenous toxicant substances and end-products of metabolism from the body, encompassing a process known as biotransformation, whereby fat-soluble substances are converted to water-soluble molecules to facilitate elimination from the body. It is an essential, yet complex, process that occurs continually throughout the body, which may be heavily burdened during sport or exercise in certain individuals, particularly those who undertake strenuous or ‘excessive’ training. As such, it is important for a health practitioner to be able to determine the detoxification load of an individual athlete, plus understand the nutritional resources available to support biotransformation within the body. This chapter provides an overview of the main detoxification processes, along with a comprehensive review of nutritional and lifestyle considerations to support an athlete’s inbuilt detoxification and biotransformation processes.