System users are typically defined in /etc/passwd file, but this isn't necessary. Using NSS you can configure the lookups to be done from elsewhere (e.g. LDAP). See passwd userdb configuration for how to set this up. Especially if you're using nss_ldap you must set blocking=yes.
System users usually have their own separate user IDs (UIDs). This is good from security point of view, because it means that the kernel will also prevent users from accessing each others' mails.
If the users have direct write access to the mail files (eg. the users have shell access), they can easily cause all sorts of mailbox corruptions. That may generate all kinds of error messages to Dovecot's error logs, so it may be sometimes difficult to tell if there really is a problem or if user is just doing something stupid.
If users are going to access the mailboxes with other software than Dovecot, it's important to make sure that their mailbox accesses are compatible. This mostly means that with mboxes you must make sure that everyone uses the same locking methods in the same order.
Admins often wish to use different passwords for IMAP and POP3 than for other services (eg. SSH), because IMAP and POP3 clients often send the password unencrypted over the internet without even bothering to give users any warnings. Dovecot can easily support non-system passwords for system users.
If you wish to use system passwords, you'll want to use one of these passdbs:
PAM: Most commonly used in Linux and BSDs nowadays.
BSDAuth: BSD authentication is used by OpenBSD.
Passwd: System users (NSS, /etc/passwd, or similiar). This may work instead of PAM (mostly in some BSDs).
Shadow: Shadow passwords for system users (NSS, /etc/shadow or similiar). Deprecated by PAM nowadays, but it should work with Linux and Solaris.
Usually UNIX systems are configured by default to deliver mails to /var/mail/username or /var/spool/mail/username mboxes. You may decide to use these, or use maildir format instead.
Dovecot detects the mailbox format and location automatically if mail_location setting isn't set, but it's still a good idea to explicitly tell Dovecot where to find the mails. This makes it sure that Dovecot behaves correctly also when the user's mailbox doesn't exist at the moment (eg. a new user). If Dovecot can't figure out where the existing mails are, it simply gives an error message and quits. It never tries to create a missing mailbox when autodetection is used.
See MailLocation for more information how to configure the mailbox location. Below are the highlights for mbox and maildir.
The /var/mail/username mbox is called user's INBOX. IMAP protocol supports multiple mailboxes however, so Dovecot needs some directory where to store the other mailboxes. Typically they're stored in ~/mail/ or ~/Mail/ directory. All of these locations are included in mailbox location autodetection. You can specify them manually with:
mail_location = mbox:~/mail:INBOX=/var/mail/%u
Remember that the first path after mbox: is the mailbox root directory, never try to give mbox:/var/mail/%u because that just isn't going to work (unless you really want to store mails under /var/mail/%u/ directory).
If you're also using other software than Dovecot to access mboxes, you should try to figure out what locking methods exactly they're using and update mbox_read_locks and mbox_write_locks settings accordingly. See locking section in mbox for more information.
Maildir is typically stored in ~/Maildir directory. You can specify this manually with:
mail_location = maildir:~/Maildir
Dovecot, including several other software, allow using "/./" in home directory path to specify the chroot path. For example /home/./user would chroot to /home. If you want to enable this for Dovecot, add the chroot path to valid_chroot_dirs setting (/home in the previous example). If this isn't done, Dovecot just ignores the "/./".