In populations receiving highly active antiretroviral therapy (HAART), the incidence of non-Hodgkin's lymphoma (NHL) has decreased by less than other AIDS-associated illnesses. In Australian AIDS-registration data, NHL has decreased by 37.5% since 1994, compared with a 55% decrease for other AIDS-associated illnesses (p = .033). Three factors may contribute to this discrepancy. First, in contrast to most other AIDS-associated illness, molecular and epidemiologic evidence suggests that there is no single organism that causes AIDS-related NHL. Thus, the HAART-induced partial recovery of reactivity to foreign antigens may be relatively ineffective in NHL prevention. Second, with the exception of primary NHL of the central nervous system, AIDS-related NHL tends to occur at a less advanced stage of immune deficiency than other AIDS-related diseases; therefore, the HAART-associated partial recovery of the immune system may be insufficient to prevent NHL. Third, it is unclear whether HAART is fully effective at reversing the B-cell stimulation that is associated with HIV infection and is a risk factor for NHL. Unless more complete immune reconstitution can be achieved, it is likely that NHL will become proportionately more important as a cause of morbidity and mortality in people with HIV and AIDS.