Highly active antiretroviral therapy (HAART) has dramatically improved the prognosis of patients with HIV. Low adherence and toxicity among HIV-positive patients starting HAART, however, can lead to discontinuation of therapy and limit long-term treatment success. Moreover, increasing prevalence of primary resistance (>10%) as well as the accumulation of mutations resulting from continued selection pressure exerted by ongoing antiretroviral treatment in patients failing virologically, mean that new compounds are needed that retain antiretroviral activity against resistant strains. Tipranavir (Aptivus ®) is a novel protease inhibitor (NPPI), which is characterized by a unique genetic resistance profile that allows it to remain active against HIV strains resistant to currently licensed protease inhibitors (PIs). Tipranavir was approved and licensed in the US and Europe in 2005 for treatment-experienced patients. This review summarizes the currently available data and studies on tipranavir and discusses the possible position of tipranavir in the currently available armamentarium of antiretroviral drugs.