The use of highly active antiretroviral therapy during pregnancy has reduced the prevalence HIV of mother-to-child transmission (MTCT) dramatically. At present, the recommended first-line treatment for prevention of MTCT in developed countries is protease inhibitor-based highly active antiretroviral therapy. In this review, we give an update on the pharmacokinetics of the protease inhibitors used during pregnancy and its clinical implications.Protease inhibitor-based highly active antiretroviral therapy is generally safe for mother and child and has been proven to be effective in reducing MTCT. Although no major safety concerns have been raised so far, the effect from protease inhibitors on preterm labor remains controversial. During pregnancy, drug disposition is affected, but not to the same extent for each protease inhibitor. The clinical relevance of the reduced exposure during pregnancy needs further investigation. There are no data for the new generation protease inhibitors.Protease inhibitors are currently the best option when it comes to treatment of pregnant HIV-infected women and preventing MTCT. Although all tested protease inhibitors generally showed good data, boosted saquinavir and atazanavir seemed to be less affected by pregnancy and can therefore be considered as the first choice to be used for preventing MTCT. However, it is essential to generate more data to support this recommendation. Because the observed lower exposure in some women, therapeutic drug monitoring is indicated during pregnancy.