If you are using any of the "signed" APIs you will need to have the application signed before it will run on commercial hardware.
Once you have paid for your API signing keys, there is no real downside to signing the application for testing on the device. I often do this several times a day as there are certain functions that can really only be tested fully on the device. While there is a theoretical limit to the number of times you can use a signing key, RIM seems to set the counter so that limit is 2^32-1
Signed APIs are identified in the Blackberry API documentation with a Padlock icon which hyperlinks to the text note included below. There are many. AESCryptoToken is one example. The method documentation will include this note:
Signed: This element is only
accessible by signed clients. If you
intend to use this element, please
contact RIM to establish the necessary
agreements that will allow you to have
your COD files signed. Signing is only
required for use on the device,
development under the JDE can occur
without signing the CODs.
You may also come across the Certicom Cryptography APIs which require a separate signing key. I haven't been able to locate an exhaustive list of signed APIs.