'The only true wisdom is in knowing you know nothing.' - Socrates
The other night, my best friend Chris commented to me in a chat that he was sometimes amazed at how I knew so many things about the game of DnD. I was curious as to what he meant, so I asked for an example. He went on to talk about a particular encounter where essentially I had to make a ruling as a DM. From his perspective, I made this ruling based on some obscure knowledge of the volumes upon volumes of text available to me in rulebooks. In truth, I simply don't have time to dig up every little particular rule of the game, and most of the time, I simply make rulings on the fly, a trait common to those players and DM's who would usually consider themselves to be of an "old school" mentality, I suppose.
The first, and most important piece of advice I tell anyone interested in game mastering a RPG, is to realize that you know nothing about the game. Not only should you realize this, you should embrace this philosophy. The rule books are there to be a guide first and foremost, but the DM is the final say at the table on any ruling. That is not to say that a DM should not look through and utilize any of the rules in the DMG or any other supplemental book. Rather, this philosophy simply means that you don't rely on these books for every little thing that pops up. They are meant to serve as a guide, not a crutch.
New DM's are often terrified at the notion of sitting at a table, having prepared what they think to be a well planned adventure, only to have a player do something out of the ordinary, requiring a ruling. I know, because I have been there myself. Having 3 or 4, or sometimes even more, people staring you down and waiting for you to come up with something can be a lot of pressure. Immediately, the new DM feels the need to whip out a book to make sure he/she "gets it right." Resist this urge. Think about the situation, utilize the stats available, along with the circumstances, and make a ruling. Because if you pull out that book, and start digging, the rules lawyers at the table are going to expect you to do that every single time something out of the norm pops up. Unless you just started playing RPG's yesterday, you know that "things out of the norm" are essentially THE norm at the game table. You have to be prepared to make judgments on the fly, and be willing to make those judgments.
Yes, having a firm grasp on the DMG will make it a lot easier to make good judgments, but in the end, you are the DM. As long as you remain impartial to the players and the game, the rulings you make will be fair. I have never had one of my players question me on a ruling in a game, or somehow perceive that I was "out to get them." That is not to say that the DM should never be willing to listen to a player on a subject. If what he/she says makes sense, or seems the best way to handle it, use it to make your ruling. Remember, as a DM, your first, and most important function, is to create a living and breathing world of adventure for the players to explore. This is where the DM should focus most of their time, as opposed to learning every little penalty associated with exceeding a certain character's encumbrance by one pound.
As a new DM, once you make the realization that you don't know anything, and don't have to know everything, the game will begin to open up in a variety of ways. Realize and embrace the fact that you know nothing.