Opioid dependence remains the main type of illicit substance used in Malaysia, which has an estimated 187 771 opiate users. There are currently 333 active methadone maintenance treatment centres nationwide. Although methadone has proven to be an effective maintenance therapy, it has clinical concerns which can have an impact on its effectiveness and safety.A case series of seven patients from Malaysian private and public hospital settings who had an adverse reaction with methadone is discussed.Despite methadone being an effective therapy for opioid dependence, there is a need for other alternative effective therapies, such as naltrexone, buprenorphine and the co-formulation of buprenorphine-naloxone, to be made available to physicians in both public and private sectors. There is need for individual treatment consideration to avoid adverse effects, drug-drug interactions, overdosing and in the presence of co-morbidities. An emphasis on safe storage of takeaway methadone is also needed. [George P, Vicknasingam B, Thurairajasingam S, Ramasamy P, Mohd Yusof H, Yasin MABM, Shah ZUBS. Methadone complications amongst opioid-dependent patients in Malaysia: A case series. Drug Alcohol Rev 2018;37:147-151].