"We must use time as a tool, not as a couch."
--John F. Kennedy
Many presses have a clearly advertised reading season. If you are sending blindly--that is, not from an ad, make sure you send to them when they are actually reading manuscripts. Some presses read for only one month out of the year. Any of the reference sources previously mentioned will give you this information.
DVICE. Summer is the worst, especially for small presses and any publishing concern connected to universities. If you send at the wrong time, your manuscript is likely to be catalogued by a secretary or student worker and put into a pile to wait for as long as it takes. They assume that you know what you're doing. Just as often, however, your manuscript will be returned to you unopened. This is not rudeness on their part. Rather, it is naivete on yours.
Also, about your work. Send your work when it's finished--that is, when it's the best you can do right now, not the best it can ever possibly be, which is a frame of reference that has no end.