Although the term substance can refer to any physical matter, substance abuse has come to refer to the overindulgence in and dependence of a drug or other chemical leading to effects that are detrimental to the individual's physical and mental health, or the welfare of others.

The disorder is characterized by a pattern of continued pathological use of a medication, non-medically indicated drug or toxin, that results in repeated adverse social consequences related to drug use, such as failure to meet work, family, or school obligations, interpersonal conflicts, or legal problems. There are on-going debates as to the exact distinctions between substance abuse and substance dependence, but current practice standard distinguishes between the two by defining substance dependence in terms of physiological and behavioral symptoms of substance use, and substance abuse in terms of the social consequences of substance use.

Substance abuse may lead to addiction or substance dependence. Medically, physiologic dependence requires the development of tolerance leading to withdrawal symptoms. Both abuse and dependence are distinct from addiction which involves a compulsion to continue using the substance despite the negative consequences, and may or may not involve chemical dependency. Dependence almost always implies abuse, but abuse frequently occurs without dependence, particularly when an individual first begins to abuse a substance. Dependence involves physiological processes while substance abuse reflects a complex interaction between the individual, the abused substance and society.