There can come a time when our understanding requires a complete revision of what we know. When Einstein merged space and time into Minkowski space-time that was the end of Newton. Blame A. Graham Bell, blame Faraday, blame Henry Ford. Einstein did not have the final word, which even he knew. It might be that nobody will ever have the final word, although they are trying to minimize the number of dimensions. Planck is to be launched in 2007, and who knows what it might see beyond what the WMAP has seen?
What killed Newton was the observational evidence (constant lightspeed, null Michelson-Morley, perihelion precession and stellar aberration).