The Plasmodium parasite successfully infects and replicates in both human and insect vectors. Population studies in humans have long detected the enormous selective pressure placed by the parasite on its human host, revealing the footprints of co-evolution. Available complete genomic sequences for the human and insect hosts, and additional sequences from multiple field isolates of Plasmodiumfalciparum have identified a wide array of protein and gene families that play a crucial role at the interface of host-parasite interaction. Selected examples of such interactions will be reviewed herein.