Human and mouse genetic studies have led to significant advances in our understanding of the role of voltage-gated sodium channels in pain pathways. In this chapter, we focus on Nav1.7, Nav1.8, Nav1.9 and Nav1.3 and describe the insights gained from the detailed analyses of global and conditional transgenic Nav knockout mice in terms of pain behaviour. The spectrum of human disorders caused by mutations in these channels is also outlined, concluding with a summary of recent progress in the development of selective Nav1.7 inhibitors for the treatment of pain.