Together with the pore-forming protein perforin, the family of granule-bound serine proteases known as granzymes forms an antiviral arsenal central to the function of cytotoxic T lymphocyte (CTL) and natural killer (NK) cells. The prevailing view is that perforin facilitates entry of granzymes into the cytoplasm of a target cell, where they access their substrates to trigger cell death (Voskoboinik et al., 2006). Humans and rodents have three granzyme subfamilies encoded on distinct chromosomal loci: (1) granzymes A and K have trypsin-like activity; (2) granzyme M cleaves after unbranched hydrophobic residues; and (3) human granzymes B and H and rodent granzymes B through G have chymotrypsin-like activity. Although there is no doubt that granzyme B plays an important role in inducing apoptosis, and it is generally accepted that granzyme A can trigger a distinct nonapoptotic form of cell death, the cytotoxicity of other granzymes is less certain. Over the years, a number of other functions have been suggested for granzymes, but few studies have dealt with these topics, particularly of late.