The host protein SAMHD1 has been identified as the first mammalian deoxynucleoside triphosphate triphosphohydrolase(dNTPase), which blocks the infection of HIV-1 in non-cycling immune cells. SAMHD1 protein is highly expressed in human myeloid-lineage cells and resting CD4⁺T lymphocytes, which restricts HIV-1 replication by hydrolyzing the cellular dNTPs, thus inhibiting reverse transcription and viral complementary DNA(cDNA) synthesis. Recent studies have revealed that SAMHD1 plays an important role in virus whole life by promoting HIV-1 genome recombination, degenerating viral genome RNA and restricting virus transmission between cells. In this review, these progress on SAMHD1 research are summarized and the mechanisms by which SAMHD1 mediates retroviral restriction are analyzed.