Extensive genetic polymorphisms in Mus spretus have ensured its widespread use in many areas of genetics. With the recent increase in the number of single nucleotide polymorphisms available for laboratory mouse strains, M. spretus is becoming less appealing, in particular for genetic mapping. Although M. spretus mice are aggressive and poor breeders, they have a bright future because they provide phenotypes unobserved in laboratory strains, and tools are available for modifying their genome and dissecting the genetic architecture of complex traits. Furthermore, they provide information on fundamental genetic questions, such as the details of evolution of genomes and speciation. Here, we examine the use of M. spretus from these perspectives. The impending completion of the M. spretus genome sequence will synergize these advantages.