The consumption of alcohol, tobacco, and other drugs has become a concern in high-performance athletes. Professional athletes are more exposed to drugs than the general population. Although some drugs are unquestionably detrimental to performance, several studies have nevertheless shown evidence of increased consumption of these substances within this sub-population. This review aimed to elucidate alcohol, tobacco, cocaine, cannabis, and opioid use among high-performance athletes, discussing the prevalence of substance use, its impacts, and alternatives to treatment in this special population. Unfortunately, no clinical trials for the treatment of substance use disorders were carried out with this specific sub-population. Therefore, the strategies adopted for the general population should be adapted to high-performance athletes. Psychological, psychosocial, psychoeducational, cognitive-behavioural, motivational interviewing approaches can be implemented. As regards pharmacological treatment, medications used in the treatment of alcohol and tobacco dependence, such as naltrexone, disulfiram, acamprosate, varenicline, bupropion, and nicotine replacement treatment can be used without problems. However, some medications used in cocaine and opioid dependence treatment, such as moldafinil and methadone, are prohibited by doping enforcement agencies. Professionals involved with athletes should be aware of the signs and symptoms of the acute effects of substances so as to enable an early identification of substance abuse problems, especially during training periods.