The literature review was planned to discuss the extent of opioid, alcohol and methamphetamine use disorder in Pakistan, the neurobiology of opioids, alcohol and methamphetamine, the importance of medication-assisted treatment and recommendations for Pakistan. A PubMed literature search was conducted and newspaper articles were also reviewed. In per capita terms, Pakistan is reported to be the most heroin-addicted country in the world. Pakistan has a significant alcohol abuse issue as well. The newest epidemic is that of crystal methamphetamine or “ice” which is consuming the youth and urban elite. There are long-term structural and functional changes in the opioid-addicted brain and factors that influence the vulnerability to addiction. The genesis of Pakistan’s opioid epidemic is critical to understand as the country became victim to the proximity to, and politics of, Iran and Afghanistan. There is poor resource allocation for the treatment of substance use disorder, especially in comparison to what is spent on counter-terrorism. Addiction has had a devastating effect on children and the youth of Pakistan. It is vital to recognise addiction as a chronic disease comparable to diabetes, hypertension and asthma; and not a personal weakness. Medication-assisted treatment includes using buprenorphine-naloxone and naltrexone for opioid use disorder, injectable naltrexone for alcohol use disorder, and mirtazapine and bupropion for amphetamine use disorder. Coordination between the healthcare system, the Anti-Narcotics Force, the pharmaceutical industry and parliament is important. A university-affiliated addiction centre should be developed so it can provide guidance with research and treatment. Buprenorphine-naloxone and injectable naltrexone are urgently needed at an institutional level for the treatment of opioid and alcohol use disorder.