Due to the closer virus-host interactions viral diseases are more difficult to control by drugs than most of the bacterial infections. Moreover, the search for antiviral compounds against HIV is an exceptional challenge. The enormous genetic and biological variability, the life-long persistence and the invasion of the brain are only some of the aspects which complicate a fast solution. In principal there are three different strategies to develop new chemotherapeutics. Most of the drugs so far tested in clinical trials were identified by routine screening, others were modified by specific chemical synthesis. After the three-dimensional structure of some HIV proteins became known, rational drug design by computer modeling resulted in compounds exhibiting excellent anti-HIV activity in vitro. The reverse transcriptase inhibitor AZT has been used for HIV-infected individuals for several years. However, side effects and the development of AZT-resistant virus strains force to combine AZT with other drugs and to develop additional lead compounds.