Lentiviruses belong to a subfamily of the retroviruses usually associated with persistent infections in animals and humans. They have complex replication cycles involving numerous regulatory and accessory proteins, which sets them apart from the oncoretroviruses and spumaviruses, the two other main subfamilies of the retroviruses. Studies over the years have elucidated the various molecular mechanisms involved in the replication of lentiviruses. The first step involves the fusion of the envelope glycoprotein (gp120) to the host cell membrane followed by entry of the virus into the host cell. Immediately following viral entry is reverse transcription, integration, gene expression, encapsidation, budding and lastly virus maturation. This review focuses on the molecular mechanisms involved in the lentiviral replication, using human immunodeficiency virus type I (HIV-1) as an example.