The generation of small animal models, which preserve the ability for the generation of primary and memory immune responses of the engrafted human immune cells and in which a robust HIV-1 infection may occur, may enable the rapid screening, development and evaluation of HIV-1 protective vaccines and adjuvants. This manuscript reviews the existing mouse HIV-1 models used to study virologic, immunologic and pathogenic aspects of HIV-1 infection and disease and discusses their limitations and advantages, especially in the context of vaccine development, with special focus on the recently developed Trimera-HIV-1 animal model.