If you're working with texts listed in the title (the targumim, Mishnah, Talmudim, etc.) Jastrow is a must despite it's defects; there isn't really anything comparable for the English speaker that's readily available. Still, if you have to use it, you should be aware of certain points:
1) It's dated: The dictionary was originally published around the turn of the 20th century, and predictably does not reflect subsequent research.
2) Jastrow's etymologies can be wonky: Be careful, keep you eyes open, and it you find yourself forced into an odd reading or an unbelievable root is suggested, double check against another source.
3) Entries are listed left to right: This might not be so bad if you don't have much experience with Hebrew books, but it can be quite disorienting otherwise.
4) Avoid the single-volume reprints: Yes, I know, the two-volumes-in-one reprints are cheap and everywhere, but the quality of the print can be quite low in these things, as well as reduced in size. If one plans to do extensive work with Jastrow ready at hand, consider forking out the extra cash for a used copy in two volumes. I acquired mine in the 90's very cheaply because it thrashed. I had it rebound for about the price of a new scholarly book, and it has served me faithfully since. ( )

Two volume set in one binding. Slip Case.Schollarly . In both Hebrew and English. ( )