Any potential therapeutic use of germline genetic interventions seems to bring with it questions about which genetic variants are pathogenic and which are normal; what normal variation in the human genome is; how we fix reference sequences for important genes and how we measure individual variation against these sequences; and what traits we think warrant genetic intervention. There is, it seems, simply no way to think about germline genetic interventions without raising questions about which genes, which conditions, and which aims the technology should target. This chapter lays out and explores the targets problem for germline genetic interventions: the problem of determining which genes are justifiable targets of germline genetic interventions, and what criteria can be utilized in some future version of reproductive medicine that could include germline intervention to separate permissible from impermissible targets.