From the misc.transport.road FAQ:

There's a very strict plan for numbering Interstate routes. The one and two-digit routes are the mainlines, with the even numbered routes going east-west, and the odd routes going north-south. The even routes' numbers increase as you go north, with the odd Interstate roads increasing to the east. The major routes end in 0 or 5. As for three-digit interstates, those that both start and end at a 2-digit route get an even first digit, while those with a dangling end or ends have an odd first digit. Some states do this differently; even 3dis usually return to the parent. California is an example. The last two digits are the parent 2di.

Q: What happened to letter extensions on Interstate highways?
A: AASHTO banned them in 1980 and told state DOTs to think of other numbers. Two still remain on I-35. I-15E in California stayed until 1982.

Q: Why does I-35 split in Dallas and Minneapolis?
A: As stated in the previous question, some Interstates once carried letter suffixes. All but two were changed in 1980. Those two are the I-35 splits in Dallas and Minneapolis, which remain because there was no consensus on what the new numbers would be. The smaller cities, St. Paul and Fort Worth, did not want their Interstate highways "demoted" to 3di's.

Q: Why the heck does I-99 have such a weird number?
A: This has been one of the most contentious questions or topics on the roadgeek newsgroups. Unlike other interstate highways, which have their numbers assigned by AASHTO, I-99's number was assigned in a piece of appropriations legislation sponsored by Rep. Bud Shuster (R-Pa.), through whose district the highway runs. Many of the regulars on m.t.r. and #roadgeek take issue with this highway designation because:
1) Its number was written into law, as described above;
2) Its number is out of place--a highway designated as I-99 should run right along the Atlantic coast; and
3) From its length (under 70 miles), location (in an area where all the available 2di designations are already being used), route (basically, a spur from I-76 to the Altoona/State College area, at least until it connects to I-80), and the fact that it doesn't come close to any interstate other than I-76, an odd 3di designation (such as I-576) would be more appropriate.
As a side note, I-99 also has the distinction of being the only 2 digit interstate that does not have a direct interchange with any other interstate.
More information is available at http://www.pahighways.com/IHwys/I99.html.

Q: What is I-238?
A: Interstate 238 is a 2-mile freeway near Fremont, California. It is not numbered according to the regular Interstate numbering conventions, rather, it was an extension of CA 238. There is no I-38. More information is at http://www.gbcnet.com/roads/I-238/.

Q: Why are there two Interstates 76, 84, 86 and 88?
A: All duplicates but 86 arose when most letter suffixes on Interstates were removed in 1980. Eastern I-86 was recently added because there were no other choices that would fit. At one time, an eastern I-86 existed from Hartford, CT to I-90 in MA; this is now part of I-84. There was also a duplicate I-39, but it is now signed along I-90.