Hepatitis C virus (HCV), a positive stranded RNA virus of the family Flaviviridae, is the major cause of non-A, non-B hepatitis worldwide. The HCV genome encodes a precursor polyprotein of ~ 3,000 amino acids that is processed co-translationally and post-translationally to give rise to viral structural and non-structural proteins. Nearly all of these viral proteins have been shown to modulate cell death via various mechanisms. In addition, studies using the replicon and recombinant HCV cell culture systems have yield important insights into the modulation of programmed cell death by HCV replication. Here, we summarize current knowledge on the modulation of apoptosis and other programmed cell death pathways by the HCV in these cell culture systems.