The DNA integration step in the replication cycle of the human immunodeficiency virus (HIV) has been recognized as an important target in antiviral strategies. There are two main reasons for this. First, integration of HIV DNA into the human genome is required for replication of this retrovirus. Second, since the integration reaction does not have an obvious cellular counterpart, drugs that specifically inhibit integration may not be toxic for the cell. Here, we focus on the only protein known to be required for retroviral integration, the integrase (IN) protein.