Viruses are obligate parasites of cellular hosts and therefore are constantly confronted with the host immune system. Evasion of innate immunity mechanisms by viruses is paramount for the establishment of their infection. The complement system can directly neutralize viruses and also augments adaptive immune responses against them. This system, therefore, is central to host innate immune surveillance, and viruses have evolved a multitude of ways to escape its assault. A major strategy employed by viruses is the molecular mimicry of human complement regulators, namely regulators of complement activation (RCA) proteins and CD59. Herein, we outline up-to-date information on the structure, function and role of viral homologs of the human complement regulators in viral pathogenesis.