This is just a summary of the main concepts. There are entire books (Larry's book) on the topic and it is hard to summarize in a brief article. Here are a few guidelines.
The 2 most desirable leads are:
1) Top of a sequence, preferably 3 in a row such as KQJ or QJ10.
2) Partner's suit. Lead the card you would lead even if he hadn't shown the suit (so LOW from Qxx).
Against small slams, lead aggressively (usually). This might mean leading away from an honor.
Against partscores, lead conservatively (usually). This can be a trump or a suit with all small cards.
Trump leads are okay. You should try to lead a trump when declarer has bid 2 suits and lands in his second suit.
Against notrump, usually lead your best suit (the 4th highest card, unless you have an honor-topped sequence like J109 or 1098).
Against suit contracts, a side-suit singleton is a good lead, unless you have a very strong/long trump holding.
Do not lead (nor underlead) aces against a suit contract. This applies to Trick 1 only (later in the hand, it is okay).
Yes, some of these rules conflict at times. Opening leads can be tough, yet it is so important. Try to use the above guidelines and not to get too frustrated.
More Opening Leads...
You'll never make a worse lead than this one: Fantoni Lead.
Click here for another Opening Lead Article.