In a recent interview, Valve spokesperson Doug Lombardi confirmed that they are working on a sequel to Portal and promised that it will be "significantly more than just a bunch of new puzzles".
The new Portal will definitely be released, the Valve spokesman confirmed but admitted that he doesn't know when it would do so. "There'll be more Portal, for sure. But the details of that, to be honest, we're still working out," he said.
Same thing goes for Half Life 2: episode 3. "With Episode Three we want to live up to the promise of where we are taking things to; there's a lot of work being done to make sure we deliver on that promise", stated Lombardi. "Exact details on what's next for Gordon are a way off; probably months not weeks."
The chances of having another Orange Box are slim, as all Valve projects work to independent timetables. But if several titles are finished around the same time, we might end up having Orange Box 2.