PURPOSE OF REVIEW: Scheduled treatment interruption appears to be an attractive alternative to continuous treatment in reducing side effects and costs and increasing comfort and quality of life by reducing overall drug exposure. The question is whether such an interruption is safe. The development of resistance, treatment failure, and the occurrence of diseases induced by decreasing CD4 cell counts or virological rebound are matters of concern. RECENT FINDINGS: Fixed-cycle scheduled treatment interruption and CD4 cell-guided treatment interruption have been evaluated in randomized controlled trials. Scheduled treatment interruptions, particularly guided by CD4 cell counts, dramatically reduce drug exposure by approximately 60%. The results regarding toxicity and quality of life are more confusing. Against expectations, most trials show little or no reduction in drug-related toxicity and no increase in quality of life. SUMMARY: Antiretroviral treatment interruption strategies reduce costs significantly but have inconclusive effects on toxicity and quality of life. The progression of HIV and development of resistance have been reported; therefore scheduled treatment interruption cannot be recommended over continuous treatment. Interruptions using a lower threshold of at least 350 CD4 cells/microl, lasting less than 3 months, and considering the pharmacological properties of drugs may be safe for most patients.