I do this all the time. I couldn't get DBD::Sybase to fly for me, so I use DBD::ODBC.

First, you need to get unixODBC (either from your distro's packages or from here) (I've heard that iODBC also works but I haven't tried it).

You also need FreeTDS (your distro might not package this one). When building it, you'll want to pass "--with-unixodbc" to the configure script. You might also want to pass "--with-tdsver=7.0" if you've got MSSQL 7, or "--with-tdsver=8.0" if you've got SQL 2000 (haven't tried it with 2005 but I assume it'll work with 8.0). Build and install FreeTDS, and then you can set up your configs.

Assuming you passed "--prefix=/usr/local --sysconfdir=/etc" to your configure scripts, your configs should look something like this. Adjust paths to taste.

/etc/freetds.conf

[global]

# skip misc freetds settings...

[myserver]

host = sql.example.com
port = 1433
tds version = 8.0  
# do tds version = 7.0 if SQL 7
[download]

/etc/odbcinst.ini

[FreeTDS]
Description     = FreeTDS MS SQL Server Driver
Driver          = /usr/local/lib/libtdsodbc.so
Setup           = /usr/local/lib/libtdsS.so
[download]

/etc/odbc.ini

[mydb]
Description = My Example Database
Driver = FreeTDS
Servername = myserver
# Servername should be the name of the section in freetds.conf
Databse = mydb
[download]

Then install DBD::ODBC from CPAN, and connect with DBI->connect('dbi:ODBC:mydb', $username, $password)