Flash memory supports a limited number of writes. After about 10,000 writes, you may find that it no longer allows you to write any longer. I have sucessfully killed a CF card by allowing a swap file to exist on it. Six months later, the CF card was acting like it had bad sectors. If you can ensure that you do a minimal number of writes, then you'd probably be ok. That typically means using a RAMdisk.
In Windows, the things that are heavy writers are the registry and the swap file.