African spiny mice (Acomys spp.) are unique precocial rodents that are found in Africa, the Middle East, and southern Asia. They exhibit several interesting life-history characteristics, including precocial development, communal breeding, and a suite of physiologic adaptations to desert life. In addition to these characteristics, African spiny mice are emerging as an important animal model for tissue regeneration research. Furthermore, their important phylogenetic position among murid rodents makes them an interesting model for evolution and development studies. Here we outline the necessary components for maintaining a successful captive breeding colony, including laboratory housing, husbandry, and health monitoring aspects. We also review past and present studies focused on spiny mouse behavior, reproduction, and disease. Last, we briefly summarize various current biomedical research directions using captive-bred spiny mice.