The Montreal Protocol has controlled the production and consumption of ozone-depleting substances (ODSs) since its signing in 1987. The levels of most of these ODSs are now declining in the atmosphere, and there are now initial signs that ozone levels are increasing in the stratosphere. Scientific challenges remain for the Montreal Protocol. The science community projected large ozone losses if ODSs continued to increase, and that ozone levels would increase if ODSs were controlled and their levels declined. Scientists remain accountable for these projections, while they continue to refine their scientific basis. The science community remains vigilant for emerging threats to the ozone layer and seeks scientific evidence that demonstrates compliance with Montreal Protocol. As ODSs decrease, the largest impact on stratospheric ozone by the end of the 21st century will be increases in greenhouse gases. The associated climate forcings, and the human responses to these forcings, represent major uncertainties for the future of the stratospheric ozone layer.