We will be staying a week in Montepulciano beginning mid-next week (Wed-Wed)! Can any experienced travelers to this region recommend a good itinerary for day trips from this location?! We'd like to focus on just one "thing" or area a day since our one-year old and two-year old don't like to run around too much (and NO, unfortunately, it's not an option not to bring them)!

I see there are already recommended restaurants for Montepulciano listed so I will take note of those!

As already noted elsewhere, ignore Carll.

The "usual suspects" in Tuscany are Siena, San Gimignano, Montalcino, Pienza.

srice_53098,
Ask at the villa or apartment where you are staying about a wine tour (everyone in Italy has a favorite), they should set you up with a tour of a Vin Noble vineyard (probably one of the top three wines in Italy). An easy drive down A1 (autostrada) will take you to Orvieto (this is in Umbria) nice hilltown with a great white wine (Orvieto Classico), take the underground tour (tickets at the tourist office, ask them about a wine tour). About a half hour south of Orvieto is Civita di Bagnoregio a quickly fading ancient town (see Rick Steves for info)
The road from Montepulciano to Pienza (famous for cheese but has good tourist sites and nice places to eat - try Latte de Luna) to San Quirico d'Orcia (worth a stop) ends at State strada 2 (SS2) also called Cassia. South on SS2 from San Quirico (about ten minuites) you reach Bagno Vignoni (roman bath - worth a quick stop). North on SS2 (about ten minuites) you come to the turn off for Montalcino (about ten minuite up the hill). Montalcino (and around) is worth an all day visit, I stayed there for three weeks one time. At the rocca (the fortress) you can sample all the Brunello wines (arguably the top wine in Italy) as well as tour the castle. Try the wild boar and white beans at the Osteria de Cassia (cheap meal). From the circle by the rocca take the road to Sant' Antimo(about 7 Km), after three km is the village of la Croce take a left and drive thru the town (about 150 meters) La Crociona has wine tasting (this is my favorite), the restaurant in town is very good (moderate price). Continue down the road to Sant'Antimo about one km farther you come to the turn off for Barbi (the farm not the doll). Barbi has a pretty good wine (they have tastings) and a good restaurant (little more than moderate). Sant'Antimo is famous for Gregorian chants by the monks (and the fact that the church is over a thousand years old).
Also in the area is Banfi castle (from the circle by the rocca take the road to the right-up the hill-from the road to Sant"Antimo) they have wine tastings and also a restaurant (need reservations and lots of euro).
Farther north on SS2 (about 5 minutes) is Buonconvento. The old section about two minutes west of SS2 is nice but small, several good restuarants here.
Just before you leave Buonconvento there is a turn-of to the east for Monte Oliveto Maggiore (about 10km ) famous for frescos by Signorelli and Sodama. There is an OK restaurant there and it is worth the trip.
West of Buonconvento (about 25 km) is Murlo a restored medieval town.
Speaking of restored medieval towns check out Monticchiello (about half way between Montepulciano and Pienza.
The above is from memory your milage may differ. e-mail if I can help.

Yes, what he said. ;-)

There's also Chiusi, Castiglione del Lago, Cortona, Arezzo, and even Perugia. All of these can be reached either by car or train/bus, although it's a schlep to do so by train/bus. Perugia is the farthest, about an hour by car or 2-3 by train/bus. Each of these cities has its own reasons for visiting them. With two toddlers, Cortona may be difficult since most of its streets seem to be oriented at a 45-degree angle vertically.

But let me give my standard spiel here though. DON'T try to see something every day. Leave at least one day, and preferably at least two days, for doing NOTHING. Enjoy Montepulciano without going anywhere farther than the top of the campanile of Palazzo Municipio or the tea room in Caffe Poliziano. Go to the Gattavecchi wine cellar and buy LOTS 8-) of Vino Nobile. Go to Conad grocery store down at the bottom of the hill and buy some groceries and catch the yellow mini-bus up to your apartment. If you're lucky, one afternoon you may catch the bread delivery man driving by. Above all, pretend that you're a real Poliziano resident.

Search under Stu Dudley to find a wonderful driving itinerary in that area.

Thank you all VERY MUCH for taking the time to respond to my request. We need all the help we can get!

If you follow Henry's advice you'll have great time. A few things to add; if you like roast pork Latte Di Luna's roast suckling pig is fantastic. Beside the abbey at Monte Olivetto it is in the area calledd the Crete Sense. Which is the area where ground erosin creates these very interesting & unique landscapes. Be on the lookout for lots of pheasants in the area.

If you eat at La Grotta, which is very good, in Montichiello, you'll be able to eat on a terrace that ovelooks the lowlands below and Pienza. On very clear days San Quirco & Montalcino
.
San Quirco is worth a visit, less touristy & more laid back then the other hill towns. The people were very nice & friendly.

Cortona is just under a hour from Montepulciano. I thought it would be full of "Under the Tuscan Sun stuff, (why I didn't visit there before my last trip) but it wasn't. It was a very charming town. If you can, arrive early in the morning before the fog lifts. Take the steps and streets directly up to the top of the town and enjoy being above the fog that covers the valley. Feels like your above the clouds. As the fog breaks, the surronding area comes into view. Slowly make your way down to the main piazzas as the morning progresses. There's a nice very old residential community up there which is also nice to walk around and soak up.