In response to antiretroviral therapy, some patients experience what has been termed a discordant response, characterized either by a sustained CD4+ cell count rise despite persistent viraemia or by HIV-1 RNA plasma levels below the limit of detection accompanied by a blunted CD4+ cell count response. In part because of a lack of universally accepted definitions, published estimates of the frequency of discordant responses vary considerably. Little is known about the pathogenesis of discordant responses, which seems to depend on the interaction of a multitude of viral, host and treatment-related factors. Available evidence indicates that discordant responses are associated with an intermediate risk of death or clinical progression. At present, recommendations for the clinical management of patients with discordant responses to antiretroviral therapy are largely based on observational, uncontrolled data. The development of standardized and universally accepted definitions of discordant responses is necessary to allow meaningful comparisons between studies to be made, as well as to help in the design of trials of possible therapeutic interventions.