Until the end of the 1970s, the mainstays of antiviral chemotherapy were nucleoside analogues that targeted virus polymerase, in particular, the herpesvirus DNA polymerase. The scourge of HIV triggered an unprecedented commitment to identify novel antivirals, and these efforts transformed antiviral therapy into the modern, sophisticated treatment form described in this book, with targets such as the reverse transcriptase and the protease as well as the entry of the human immunodeficiency virus. As the regulation of human pathogenic virus growth cycles became more understandable, the realisation grew that these pathogens had more than one Achilles heel that might be suitable targets for small molecules with antiviral activity. This chapter addresses those "other" targets as well as other approaches to the tried and tested polymerase inhibitors, the so-called non-nucleoside inhibitors of reverse transcriptase.