The Four Horsemen are reunited. Cassandra has been taken prisoner. As MacLeod makes plans to rescue Cassandra and face Kronos for the last time, Methos tries desperately to manipulate all the players so that he can, at least, survive.
Kronos' plan is revealed: he intends to use an engineered virus to wipe out most of humanity and conquer the survivors as part of an eternal empire. Methos eventually turns on his former comrades, he and MacLeod simultaneously battling Kronos and Silas to the death in their own respective fights, resulting in a double quickening between MacLeod and Methos.
Cassandra who still wanted to avenge herself upon the redeemed Methos, threatened him with Silas' axe, but Duncan demanded that she let him live. The centuries have truly changed Methos, and he had, in the end, helped to save humanity. Afterward, there is an implication that Methos had indeed manipulated events with Kronos hoping MacLeod could do what he himself could not -- take Kronos' head.
Here's the text of Revelation 6:8 from the Revised Standard Version of the Bible:
"And I saw, and behold, a pale horse, and its rider's name was Death, and Hades followed him; and they were given power over a fourth of the earth, to kill with sword and with famine and with pestilence and by wild beasts of the earth."
This episode was, in fact, the 100th produced episode of the series.