Giant ground sloths, relatives of the living South American tree sloths, lived across much of North America. The giant sloths disappeared along with the mammoths, mastodons, and many other large animals at the end of the Pleistocene Epoch.
There are plenty of physics reasons why a gigantic creature couldn't exist on our planet (let alone biological reasons), so we'll just cover a few.
First of all, something which you have mentioned already can limit size: the strength of the skeletal system. Think of how big and thick the steel I-beams in buildings are (and not just that, but they're often coated in concrete as well!). Any animal that was as big as a large building would need bones that are as structurally stable as those steel I-beams. Since bone isn't as dense as steel (bone is, on average, around 1.5 g/cm3, whereas even the low-grade steel is 7.8 g/cm3, more than five times as dense), it means the bones of an animal as large and heavy as a building would have to be much larger than the steel beams necessary for a building the same size. With all that bone to drag around, you'd weigh an awful lot!
This leads us to our next reason: energy. Animals and machines alike have to take in energy (in the form of fuel or food) in order to do work (like moving around). An organism that was too big would have to spend too much time eating! Plant-eating animals already spend most of their time consuming food, and the larger they get, the larger the quantity of food they have to eat in order to keep going. Since vegetation only provides so much in the way of nutrients and calories (energy), there is a point at which you simply wouldn't be able to keep up with the energy demands of your body. Since digestion takes time and isn't 100% efficient (some of the energy goes toward the digestion itself!), you can't get all of the energy from the food you eat, and if your body needs more energy than you can manage to eat, you can't survive. Even omnivores and carnivores have to spend a lot of time eating: though things like eggs and meat provide more energy per pound of food than plants, at a certain point you're using up more energy than you're consuming (consider how difficult it is for predators to catch their prey), and you can't survive.
Horses, a fairly large type of animal, must graze often to maintain their energy needs.
Photo by Jim Champion
Another reason is blood pressure. Blood, like any liquid, obeys the equations of fluid flow. Our hearts are the strongest muscles in our bodies because they have to pump blood all the time, and very quickly. It's a tough job. Now imagine you were hundreds of feet tall. How much harder would your heart have to pump in order to get blood all the way up to your head? Since the pressure required to pump a liquid increases with the height the liquid must be pumped, the heart of a very large animal would have to work much too hard. Ditto for the lungs - especially with all that extra weight (from bone and muscle), the lungs would have to push very hard to get air in and out of the animal's chest.
Now let's briefly consider the environment. If an animal was exceedingly tall, for instance, it would come across a few issues, namely, where to find food and how to breathe. There's not too much in the way of grazing up in the atmosphere, and if you get too high there's not much air, either! If an animal was exceedingly long or broad, its weight would be spread over a large surface area, and in order to prevent itself from buckling, it would need extra support (think of a long bridge span, like the Golden Gate Bridge, and imagine the towers were the animal's legs). But because of the nature of the local environment - trees, rivers, etc - being so long or wide would make getting around quite the endeavor.
Lastly, let's consider specifically your question about weight. If the animal could somehow have light, strong bones, could it better exist? Well, how about this: say the animal didn't have an issue with weight. Say it was light and strong and, despite being 100 meters tall, only weighed as much as three elephants. All the other issues aside (blood pressure, food consumption, etc), we still have another issue to contend with: air resistance. If the wind is blowing really hard, you might have trouble walking around. But what if you were really big, or, in other words, if you had a really big surface area? You'd simply blow away! An animal the size of a building will feel forces like a building would, but without the benefit of having a nice, deep foundation sunk into the ground. Because of wind or sun (imagine if you had a body the size of a building... you could get sunburns the size of a building, and you'd get awfully hot!) or any number of other factors, you wouldn't be able to go certain places. This could make life very difficult, if not impossible.
Now that you know a few of the reasons such a huge animal couldn't survive here on Earth, perhaps you can discover even more!
Kelly Chipps (AKA nuclear.kelly)
Department of Physics
Colorado School of Mines
Tony from Greece