Substance misuse, also known as drug misuse or, in older vernacular, substance abuse, is the use of a drug in amounts or by methods that are harmful to the individual or others. It is a form of substance-related disorder, differing definitions of drug misuse are used in public health, medical, and criminal justice contexts. In some cases, criminal or anti-social behavior occurs when some persons are under the influence of a drug, and may result in long-term personality changes in individuals. In addition to possible physical, social, and psychological harm, the use of some drugs may also lead to criminal penalties, although these vary widely depending on the local jurisdiction.

Drugs most often associated with this term include alcohol, amphetamines, barbiturates, benzodiazepines, cannabis, cocaine, hallucinogens, methaqualone, and opioids. The exact cause of substance abuse is sometimes clear, but there are two predominant theories: either a genetic predisposition or most times a habit learned or passed down from others, which, if addiction develops, manifests itself as a possible chronic debilitating disease. It is not easy to determine why a person misuses drugs, as there are multiple environmental factors to consider. These factors include not only inherited biological influences (genes), but there are also mental health stressors such as overall quality of life, physical or mental abuse, luck and circumstance in life and early exposure to drugs that all play a huge factor in how people will respond to drug use.

In 2010, about 5% of adults (230 million) used an illicit substance. Of these, 27 million have high-risk drug use—otherwise known as recurrent drug use—causing harm to their health, causing psychological problems, and or causing social problems that put them at risk of those dangers. In 2015, substance use disorders resulted in 307,400 deaths, up from 165,000 deaths in 1990. Of these, the highest numbers are from alcohol use disorders at 137,500, opioid use disorders at 122,100 deaths, amphetamine use disorders at 12,200 deaths, and cocaine use disorders at 11,100.

Public health practitioners have attempted to look at substance use from a broader perspective than the individual, emphasizing the role of society, culture, and availability. Some health professionals choose to avoid the terms alcohol or drug "abuse" in favor of language considered more objective, such as "substance and alcohol type problems" or "harmful/problematic use" of drugs. The Health Officers Council of British Columbia — in their 2005 policy discussion paper, A Public Health Approach to Drug Control in Canada — has adopted a public health model of psychoactive substance use that challenges the simplistic black-and-white construction of the binary (or complementary) antonyms "use" vs. "abuse". This model explicitly recognizes a spectrum of use, ranging from beneficial use to chronic dependence.

'Drug abuse' is no longer a current medical diagnosis in either of the most used diagnostic tools in the world, the American Psychiatric Association's Diagnostic and Statistical Manual of Mental Disorders (DSM), and the World Health Organization's International Classification of Diseases (ICD). According to the DSM, substance use disorder (SUD) is used to describe the wide range of the disorder, from a mild form to a severe state of chronically relapsing, compulsive pattern of drug taking which include cannabis, alcohol, caffeine, hallucinogens, hypnotics, opioids, anxiolytics, inhalants, tobacco, and sedatives as well as other, possibly unknown, substances.

History professor Philip Jenkins suggests that there are two issues with the term "drug abuse". First, what constitutes a drug is debatable. For instance, GHB, a naturally occurring substance in the central nervous system is considered a drug, and is illegal in many countries, while nicotine is not officially considered a "drug" in most countries.

Second, the word "abuse" implies a recognized standard of use for any substance. Drinking an occasional glass of wine is considered acceptable in most Western countries, while drinking several bottles is seen as abuse. Strict temperance advocates, who may or may not be religiously motivated, would see drinking even one glass as abuse. Similarly, adopting the view that any (recreational) use of cannabis or substituted amphetamines constitutes drug abuse implies a decision made that the substance is harmful, even in minute quantities. In the U.S., drugs have been legally classified into five categories; these are schedule I, II, III, IV, or V in the Controlled Substances Act. The drugs are classified on their deemed potential for abuse.

The usage of some drugs is strongly correlated. For example, the consumption of seven illicit drugs (amphetamines, cannabis, cocaine, ecstasy, legal highs, LSD, and magic mushrooms) is correlated and the Pearson correlation coefficient r>0.4 in every pair of them; consumption of cannabis is strongly correlated (r>0.5) with the usage of nicotine (tobacco), heroin is correlated with cocaine (r>0.4) and methadone (r>0.45), and is strongly correlated with crack (r>0.5)