Substances in general are both legal and illegal and it has very many effects both positive and negative on human health. Some of the substances like alcohol, tobacco products, cannabis, prescription medications and some of the illicit drugs also have therapeutic benefits. Substances with moderate misuse or disorder may provide some health benefits cannabidiol (CBD) has become one of the therapeutic agents in chronic pain, anxiety and inflammatory diseases. Low-level usage of caffeine is linked with increased mental awareness and helps in preventing neurogenerative diseases. Despite the potential benefits of using substances, it also has some severe consequences in terms of mental health and as well as physical health. For instance, excessive usage of addiction to alcohol may lead to severe heart problems, liver diseases and a variety of cancers among regular users. Similarly, tobacco use leads to stroke and lung cancer. Cannabis is one of the substances that may cause impaired memory and dysfunction of cognition and create long-term mental health. Overall, the individual is not only going to be affected because of the use of substances, but the societal impact among the youngsters in this current scenario is a challenging one. Substance abuse has adverse effects on individuals, and families, creating violence, social marginalization, sexual harassment, etc. In this chapter, overall details of the substances, natural and synthetic substances, their medications and their misuse, and the benefits and risks of using substances were discussed in depth.