They are quite possibly the most difficult PvE content you will face.Firstly, make sure you have Restorative Amber from the Klaxxi as your food. Some challenge mode golds come down to a few seconds, and the amber allows you to mana up to full in about 4 seconds vs about 10 for summoned food. ALSO, make sure you have flasks, buffs, AND reforge your gear to HASTE. A few ms WILL make a difference in tank survival. Make sure you have 18 sec invisibility potions, as well as full stacks of mana potions. Your talents and glyphs will vary from instance to instance. You should know by a couple of run through's what you will need to spec/glyph. I will say that the glyph of FoL is almost indispensable, as you will find yourself spamming it quite often, especially if the tank is spiky in damage. You will probably have to cycle your CDs during trash. I made sure I had Holy Avenger as an extra short CD, as the procs for Divine Purpose can be unreliable, especially given that set bonuses are disabled.
Interestingly, the most challenging part about the challenge modes are not bosses... it's the trash.Quite often, you will find yourself dpsing the bosses more than healing them. Be prepared to spend an upwards of four to five hours at a time on a challenge instance clear for gold, and be prepared for the frustration that comes from missing gold by about 10 seconds. If you're just going for silver/bronze, then don't even bother looking up strategies, as those are both extremely easy.