Methadone hydrochloride is a mu-opioid agonist that has been used for the treatment of pain and for the management and maintenance of opioid withdrawal for over 50 years. Several characteristics make methadone a useful drug. However, these same characteristics and wide interpatient variability can make methadone difficult to use safely. A MEDLINE search was conducted on publications between January 1996 and May 2001 to identify literature relevant to this subject. Those publications were reviewed, and from them, other literature was identified and reviewed. Published studies demonstrate methadone's efficacy in pain management and in opioid withdrawal. However, interpatient variability in pharmacokinetic variables of methadone produces difficulties in developing guidelines for methadone use. Clinicians should not be deterred from use of this drug which has been shown to benefit patients in both pain management and methadone maintenance, but an individualized patient approach must be taken to use methadone safely.