The recent West Coast experience with increased methamphetamine use is showing signs of spreading to other parts of the US. The risk of corresponding medical and psychosocial problems has led to a call to action at the highest levels of government. The next few years will likely witness a substantial increase in treatment research on methamphetamine abuse/dependence, with particular emphasis on the development and application of novel pharmacotherapies. The evaluation of these agents presupposes that we understand the clinical syndrome resulting from chronic methamphetamine use. To establish a clear picture of the biological and psychological sequellae of methamphetamine use, we compare two cohorts (500 methamphetamine and 224 cocaine users) treated at the same outpatient clinic over the past nine years, using identical manualized treatments. The results suggest that while there are important differences in group characteristics and drug effects, the total response to treatment was quite comparable.