Voltage-gated sodium ion channel subtype 1.7 (Na<sub>V</sub>1.7) is a high interest target for the discovery of non-opioid analgesics. Compelling evidence from human genetic data, particularly the finding that persons lacking functional Na<sub>V</sub>1.7 are insensitive to pain, has spurred considerable effort to develop selective inhibitors of this Na<sup>+</sup> ion channel target as analgesic medicines. Recent clinical setbacks and disappointing performance of preclinical compounds in animal pain models, however, have led to skepticism around the potential of selective Na<sub>V</sub>1.7 inhibitors as human therapeutics. In this Perspective, we discuss the attributes and limitations of recently disclosed investigational drugs targeting Na<sub>V</sub>1.7 and review evidence that, by better understanding the requirements for selectivity and target engagement, the opportunity to deliver effective analgesic medicines targeting Na<sub>V</sub>1.7 endures.