Methadone and Buprenorphine are synthetic opioids that have been used for many decades as a substitution treatment in people with opioid dependence. Sexual dysfunction is one of the most common problems in patients receiving maintenance therapy with opioid agonists. Methadone & Buprenorphine appear to have same efficacy and side effects in opioid maintenance treatment, though this is not the case for effects on sex hormones. The aim of the present narrative study is, review on articles related to effects of methadone or buprenorphine substitution on reproductive hormone profile and seminal fluid analysis in human & animal models receiving opioid maintenance treatment, and also possibility of alternating these medicines with each other. The writing of this abstract was performed using the keywords opioid, fertility, buprenorphine, seminal fluid, methadone, infertility, reproductive (sexual) hormones by searching in specific databases such as Medline, SID, Magiran, PubMed, Scopus, Science Direct. After reading the abstracts of the articles, those were not directly related to the topic in question, as well as articles with duplicate findings were excluded. Finally, data from 22 articles were used to write the findings of this summary. A review of studies showed that long-term methadone causes sexual dysfunction and infertility. Few studies on seminal fluid parameters, have shown reduced sperm motility in methadone-consuming men, may be a potential cause of infertility. Replacement of methadone with Buprenorphine in the treatment of opioid dependency, provides more options for clients and clinicians. Also, considering lower side effects, it is recommended that substitution begins with buprenorphine as the first line of treatment, and directed to methadone as the second medication if there is not satisfied respond to buprenorphine.