As far as malware goes, virtualization obfuscators are the current state of the art. They are a fundemental advancement in packing. Up until virtualization obfuscators, all other packers had the weakness where at some point the unprotected program would end up in memory. This weakness is easily exploitable (ala VxClass, see Recon 2010 for an easily digestible talk). Virtualization obfuscators are still beatable with manual reverse engineering (see Rolles WOOT 2009) and some effort has been made to automate the process (see Wenke Lee's group at Oakland 2009). But when a packing scheme forces you to hire reverse engineers who know what symbolic execution is, you know that you've substantially raised the bar.