Vpx is a protein encoded by members of the HIV-2/SIVsmm and SIVrcm/SIVmnd-2 lineages of primate lentiviruses, and is packaged into viral particles. Vpx plays a critical role during the early steps of the viral life cycle and has been shown to counteract SAMHD1, a restriction factor in myeloid and resting T cells. However, it is becoming evident that Vpx is a multifunctional protein in that SAMHD1 antagonism is likely not its sole role. This review summarizes the current knowledge on this X-traordinary protein.