The development of automated assay technology for rapid genotypic and phenotypic characterization of human immunodeficiency virus (HIV) in plasma samples now makes it feasible to use these assays in the management of antiretroviral therapy. In particular, phenotypic assays measure the drug susceptibility of the virus by determining the concentration of drug that inhibits viral replication in tissue culture. Recent experiences suggest that interpreting phenotypes may be more complicated than originally believed. Thus, rather than considering drugs as active or inactive on the basis of cut-offs, it would be more reasonable to consider their relative activity. To complicate matters further, a relatively high incidence of discordance between phenotypic and genotypic results when both tests were performed on plasma samples of antiretroviral treated patients has been reported. These findings could have considerable clinical significance, because the choice of drug regimen could differ depending on which test is used. The result of phenotypic testing may be more important when considering discordant results, because this provides a more quantitative assessment of resistance. However, clinical validation will be necessary to delineate which approach is better.