Evernote

The Evernote tagline is "Remember Everything" and it really does help to deliver on that promise.  Evernote is a combination note-taking and storing application with some great features to help categorize your notes using either notebooks and / or tags that are then easily searched.  You can quickly and easily add images, web pages, emails, and whatever you can think of in addition to basic text editing functionality.  Evernote will even scan through the images and other documents (if you want) so that everything is searchable.  As a bonus, Evernote is available on most platforms (including the Mac, web, and iPhone which are the ones that I use) and synchronizes between them all.  You can also share your Evernote libraries selectively with other folks who need to see or edit them.

I use Evernote for almost everything at this point.  On the work front, I'm using it to keep track of design decisions and brainstorming (including images of the whiteboards), take notes in meetings, track my to-do lists for everything, and keep a list of readings and technologies to follow up with (to name a few).  On the personal side of things, I keep track of other to-do lists, travel information, recipes, and my grocery list.

Evernote is also Free, though there are some bonuses for those willing to get the premium account, and I find it is well worth it.

Evernote is also extensible, and a number of 3rd party developers have put together some pretty neat solutions.  My favorite at the moment is EgretList for the iPhone.  EgretList is a to-do list manager that pulls in anything that has a checkbox from your Evernote library into a set of easily organized to-do lists that can be grouped by urgency, location, project, or whatever you can think of. 

A pocket-sized notebook

No joke, having a notebook and pen handy at all times while conceptualizing my dissertation was far more valuable than you might think. It was good for me socially as well because when an idea struck, I could jot it down rather than spending the next few hours obsessing over it. Of course, an iPhone or other PDA can help you take notes as well, but for me they are no replacement for the feel of a flair pen on real paper. You just need to be sure you don’t lose the notebooks!
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Skim

I recently discovered (as in: a colleague suggested this to me) the freeware app Skim for the mac. This is a great little tool for taking notes within a PDF file that I find much much more usable than acrobat pro. Also, the notes are stored in the file-system, not in the actual PDF so that you can then email the pdf to a colleague or student without the notes.  It supports attaching notes, highlighting, circling / labeling, a presentation mode, and a host of other handy little tricks.