The first mention I can recall of Tower Defense games is from a set of custom maps for Warcraft III: Reign of Chaos, back in the day (2002ish). For those of you unfamiliar, the basic premise is, instead of going on missions or killing your fellow players, the goal is to guard your base from rushes of "creeps" (bad guys). Wave after wave will crash into your defenses, and they have to hold. You get money for each one killed, and if some number get through to your base (usually 15 or so), you lose. Your only method of protecting yourself is building towers, which have different powers and costs.
Most of the earlier Tower Defense games were very much team-based: you had to find a total of 4, 6, or 8 players who all wanted to play the same variant. Eventually, variable number of player maps were available (I created one myself, based on the Crossfire map), and some solo ones. By far, my favorite such map was Gem Tower Defense (also available as a cheesy flash game).
Anyways, I don't always have the hours to burn on playing a long game of Gem TD, so a popular and lighter flash tower defense game comes to the rescue, especially during downtime at conferences: Desktop Tower Defense.

The game is deceptively easy, especially in easy mode. However, to do well in Normal mode and to even stand a chance in Hard mode, it helps to think about strategy a bit. The above screenshot shows some of the strategy I and others tend to use:
- Build a maze. Naturally, this is a maze building game. It is nearly impossible to win without having the enemies wind around in some death trap. For the most part, it should be constructed of the cheapest possible towers. These are pellet towers, which cost 5. They can be sold for 3 so you can put in a real tower if necessary later. You have to build a maze as well because of the "spawn" enemies: these multiply like crazy, and will easily creep through cracks in your maze, so there has to be a lot of it to catch them and kill them.
- Look at strength per dollar. One of the key points of strategy is to not build a lot of mediocre towers: you should have a lot of cheap towers, and a few very powerful towers. It's just a matter of power per dollar. For example, a bash tower costs the most, but it puts out significant damage. While pellet towers cost 5 gold, they only attack with 5 power, and they are slow. However, they are extremely powerful (and still slow) when they get their final upgrade (for a total cost of 200), where they have an attack power of 400, and the longest range of any tower (180).
- Slow tower + bash tower = obliteration of ground creeps. The bash tower has extremely high power and it can hit every single creep several times if placed optimally. Putting a slow tower near it amplifies its power significantly. Throwing an ink tower near it can also help (but be careful the ink's min and max ranges).
The site itself recommends squirt guns, but I disagree that they "upgrade well". They are useful in the early stages of the game in their weak forms, but they don't do well against dark creeps, since these are immune to weak attacks, and the squirt gun is the weakest. However, their final two upgrades significantly improve them, and make them formidable.
Anti-air are also important, since air creeps ignore your tower and just fly through, and the anti-air towers hit four at once. Their last upgrade is very expensive (over 300 gold), so I usually think it is better to have multiple less than fully upgraded anti-air towers than one fully upgraded one.
Finally, you can find inspiration from YouTube videos (just search for "desktop tower defense"), and having a look at other player's maps.

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