The River of Flame is the penultimate zone in Act 4. It can be reached by a staircase from the City of the Damned (the staircase is found near the City's waypoint).
Points of interest
The River of Flame has several points of interest. The Hellforge and Hephasto the Armorer, who drops the Catalyst of Destruction on Hatred difficulty, can be found in the first half of the area. At the end of the River lies the Chaos Sanctuary - Diablo's lair. The waypoint can be found near the middle of the River. It is here the angel Hadriel stands guard.