West Nile virus (WNv) has emerged as a new issue in the conservation of native avifauna in North America. Mortality associated with WNv infection decreased survival of female greater sage-grouse (Centrocercus urophasianus) by 25% across 4 populations in Wyoming and Montana, USA, and Alberta, Canada, in 2003. In 2004 WNv spread to populations in Colorado and California, and female survival in late summer was 10% lower at 4 sites with confirmed WNv mortalities (86% survival) than at 8 sites without (96%). We still have no evidence that sage-grouse show resistance to the virus. The 2004 WNv season was not the catastrophe that many had predicted, and the decrease in prevalence of infection and mortality in sage-grouse, humans, and horses (except in California) has left many wondering if the worst has past. Evidence suggests that risk of infection was low in 2004 because unseasonably cool summer temperatures delayed or reduced mosquito production. Moreover, mortalities occurred 2–3 weeks later in 2004 than in 2003, and the shift to later timing was consistent between years at sites where WNv reduced survival both years. Mosquito surveillance data indicated a sharp decline in prevalence and infection rate of adult C. tarsalis in southeast Alberta, the most northern latitude where WNv reduced survival, in 2003 but not in 2004. A full understanding of the implications of WNv for sage-grouse requires a long-term, coordinated monitoring strategy among researchers and a sensitivity analysis to evaluate the role of WNv in population viability. Epidemiological research examining the prevalence and ecology of the virus among reservoir hosts is crucial.