Exposure to saquinavir can be increased considerably by pharmacokinetic enhancement with ritonavir, without having a substantial impact on tolerability. Clinical trials indicate that both once-daily and twice-daily saquinavir/ritonavir treatment regimens, generally at dosages of 1,600 mg/100 mg once daily and 1,000 mg/100 mg twice daily, provide potent and sustained viral suppression and are well tolerated. In addition, data suggest that "double-boosting" strategies, including the combination of saquinavir with lopinavir/ritonavir, provide valuable treatment options in the salvage setting.