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Just What is LoL, Anyway?
Basically, it's an RTS game with RPG style elements where your team's goal is to destroy the other team's fortress before they destroy yours. Players control a single hero during the course of the game, and you'll build this hero up with skills, levels, and gear in order to achieve your goals. You can choose from a wide variety of RPG archetypes, such as tanks, healers, support, and all kinds of hybrids. You'll be traveling with "waves" of your team's minions which are constantly spawned to try to take out the opposing champions, and eventually their towers and their base. The first team to blow up the opposing base wins!
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Okay, So, How Do I Play?
First things first - It's a pretty quick download from leagueoflegends.com or you can pick up a collector's box at most stores that sell games (you get some extra stuff in there, but it's technically a Free-to-Play title). Once you've got it installed and ready to go, you'll be facing an pretty awkward Adobe Air console, but getting in a game is as easy as hitting the "Play" button on the top left and selecting to go solo with a team of people you don't know, or setting up an arranged team with your friends. But before you do that, there's some other important stuff here you should take a look at.
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Runes And Masteries
If you take a look in your player profile, you'll see that you have something called mastery trees. These are pretty much equivalent to the talent trees found in World of Warcraft and many other popular games, and allow you to "spec" you character for offense, defense, or utility. You'll receive one mastery point for every level you gain on your account (Account levels are NOT character levels, so be sure not to get those mixed up. Account levels are permanent and go to level 30, your character will have to start at level 1 each game and can go to 18).
Runes are another way to customize your character, and can only be earned by playing games, and basically allow you trick out stats that you'd like to see on your characters from game to game - Extra critical strike chance, mana regeneration, health regeneration, that kind of thing.
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It's time for your first game, and you have some choices - Pick a hero that you like (I'd definitely recommend a ranged hero for your first time out) and you'll be asked to select a couple of spells. These will act as bonus skills for your character that you'll be able to use on various cooldowns over the course of the game. When you're just starting out the choices are easy - get heal and teleport. Heal will give you the ability to heal yourself and your allies for free on a cooldown, and teleport is very useful for getting around the game field easily.
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Getting In The Game
You'll notice that the map is divided into three lanes, and you have a five man team. This means normally one person will go "solo" and the other lanes will have 2 champions apiece. Sometimes, a hero who can kill critters and creeps in the woods easily (Like Warwick) will choose to hang out in the woods and kill the NPC's there instead of sticking to a lane, essentially offering the team two solo lanes. For your first few games you'll want to purchase the items in the recommended area of the shop, this will give you some generally good gear for the hero you've decided to play.
Now it's time to develop your skills in laning - you want to stay in your lane and try to "last hit" the little minions so you'll get gold as long as you can without going back to base. This part is going to take some practice, there's no way to teach it you just have to get in there and learn the old fashioned way.
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Your First Game
After the laning period, teams will generally come together to enact what is known as a "push" on their opponents key structures and base. This is where the real crux of the game, the team fight, comes into play. Try to position yourself in a fashion where you'll be coming into the team fight firing off your critical skills at the optimum times (this is going to differ greatly depending on your hero). Either way, the game is going to be won or lost based on these fights, so make sure to play together for a better shot at a win!
Eventually, your first game will end and you'll be ready to start spending the IP you earn from playing games on runes and champions, and don't forget to add your mastery points every time you level up!