First, keep your systems patched. When Microsoft (or another operating system vendor you rely on) releases security...
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patches, test them quickly and apply them.
Second, do not run your browser or email reader from an account that has local admin privileges. A rootkit needs admin privileges in order to install malicious device drivers. Only use admin-level accounts when they are absolutely required, such as when you install new software or change the configuration of the machine. If you have a single-user machine, run the Microsoft control called the local user manager (Start, Run, then type lusrmgr.msc). This control, affectionately known as the "Loser Manager" because of the "lusr" spelling in its file name, can be used to administer accounts and groups. Create one without admin privileges, and then use that account for surfing and email.
A third way to prevent rootkit infection is to install local security tools on your machine, including an antivirus tool, an antispyware program and a personal firewall. Make sure you have all three.
A fourth category of defense only for enterprises are the so-called host-based intrusion prevention systems. Products like Cisco Systems Inc.'s Security Agent and McAfee Inc.'s Entercept, for example, monitor various applications and prevent them from making certain system calls that might be associated with buffer-overflow exploitation or the installation of a rootkit.
Beyond those preventative defenses, don't forget that there are many good after-the-fact rootkit detectors out there. These tools look for the tell-tale signs of rootkit installation, such as hidden files, hidden registry keys, and, for some of the tools, hidden processes. RootkitRevealer, from Microsoft's Sysinternals group, was one of the first of the free tools in this category of rootkit detectors. Other free products include F-Secure Corp.'s Blacklight, Sophos' Anti-Rootkit, McAfee's Rootkit Detective and Trend Micro Inc.'s RootkitBuster.
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