Quicksilver: I use this application for everything (really everything—sending quick emails, running search queries of sites like Amazon, Wikipedia, or Google, cropping photos, manipulating files, launching applications . . .).  In fact when I sit down at a Mac without Quicksilver I feel like I am working with only half a computer

DevonThink Pro:  Lots of "Brain in a Box" software out there, this is my favorite. It manages all forms of research I want to keep from web page captures and .pdfs to video and audio sources this program does it all. Plus it has some killer AI search features. The UI is ugly but apparently they are working on this for the next release.

Mellel:  For many years Microsoft frustrated me.  This word processor is built by academics for academics.  The key: the ability to separate form from content and change the entire style of the document with just a few clicks. Plus you can format text left to right and right to left in the same document.

Firefox:   I use several browsers, and not always Firefox, but this is the most reliable.

Parallels:  Now I can check how web pages look in IE without finding a Windows machine. Its like getting a windows machine for the price of a software program.

TextMate:  Good for whatever text manipulation you need, from simple mark-up to editing blog posts this application handles it all and has custom shortcuts.

WordPress: The ease of installation and active plugin community got me hooked, and I have been happy ever since.  Use it for my own blog and ones for my class.  Also related would be Edublogs, if I didn't have my own domain I would use this service (it seems like I recommend it every day to another teacher).

NetNewsWire: I think RSS is one of the most important information technologies. I haven't been able to make the shift to Google Reader like everyone else, I just prefer a desktop application.

Apple Mail:  Again while most people like gmail I prefer this Apple Program for the way it integrates with other applications (I have a gmail account I just filter it to Apple Mail).  Add in Mail-Tags and Mail-Act-On and email has never been easier.

Textpander:  Like Quicksilver I use this so often I forget.  I never type my full address, I can paste something from the clipboard automatically including link tags, it autocorrects spellings, adds in accent marks