The main downside to the Chicago Children's Museum is the crowds. It can get packed.
I actually prefer the weekend at the museum: since school groups make up much of the weekday crowd, the weekend is often not any busier, and with a much better child-to-adult ratio. School groups tend to be older and run more, so you may need to be overly protective of babies and new walkers when they come through—I’ve had multiple close calls with school kids almost running someone over.
That said, my advice is to not switch rooms when a school group arrives in yours—big school groups rarely follow the Museum Dad philosophy of taking ample time in a room. They'll usually be in and out fairly quickly. When I first started, I often left a room when a particularly big group arrived, only to find the same big group followed me to the next room a few minutes later. Now we just stay put and by the time my kids are ready for the next room, we’ve typically seen multiple groups come and go.
Fall tends to have fewer groups, spring and especially near the end of the school year tends to have the most. Summer is often even worse: area day camps will come in large quantities, but have less teacher control than school groups; the kids also tend to be older, meaning faster and bigger when they run through an area, and seemingly no less oblivious to small kids around them.
Getting to the museum early can give you some good time before the groups come in, as will using the early hour just for members on Fridays and Saturdays if you’re a member. Kids Town and Treehouse Trails seem to be the rooms that school groups inundate the most; of major rooms, they seem to spend less time in Play It Safe (the fire truck) and WaterWays. That said, Kids Town and Treehouse Trails are both too great to skip, I’d still really encourage you to visit them.
Naturally, the museum empties out quite a bit around lunch time and shortly thereafter when many kids need to nap and school groups have to leave for home. If your kids are old enough that they’re not napping, you’ll get much more space during those times.
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