Bookmarking and the History list become unreliable as these references do not include a representation of the state of the frames on the page. Frames usually have an invisible active window. Other frames become active when the mouse is clicked on it, difficult to do without a mouse. Screen readers tend to treat each frame as a separate window. This makes following the content and navigation difficult, as switching between the active frame is awkward.
Frames inherently steal real estate and cause problems for small monitors and low resolutions.
If people are using a large font they may be required to scroll horizontally to read each line of text, something that won't endear them to your site. Printing problems occur when the wrong frame is active. Links can be made to open new browser windows. Without warning this can be very confusing to the visually impaired. The future will no doubt bring more browser wars, Microsoft'isms, more advances in technology.