This paper describes trajectories of methamphetamine (MA) use among participants in a longitudinal study in rural Arkansas and Kentucky. Thirty-nine baseline qualitative interviews were conducted with active MA users. Twenty-four participants were interviewed again from 12 to 24 months later. At follow-up, 13 participants reported quitting MA use, six had reduced MA use, and five were using the drug at approximately baseline levels. Two participants had changed modes of administering MA. Health, legal, and family issues, or a combination of these factors, were linked to quitting or reducing MA use. Sixteen participants had made positive changes without drug abuse treatment, one used professional inpatient treatment, and two utilized faith-based programs. Willpower, self-isolation, staying busy, family support, and using substitute drugs were cited as strategies for avoiding MA use. The study findings have important implications for understanding rural MA use careers, guiding future research, and informing intervention strategies.