Despite the considerable efforts the treatment of metastatic cancer still remains a challenge. Cancer cells could be regarded as independent parasitic organisms with selfish trends to expand and spread in the human body. Due to the tremendous genetic plasticity they quickly acquire resistance to conventional chemotherapy and bear more aggressive and difficult to treat relapses. Oncolytic virus therapy emerges as a promising alternative approach that represents a “biological warfare” against cancer. Cancer cell are generally more susceptible to viruses of many different families as they commonly loose antiviral innate immunity mechanisms during cancer progression. Modern approaches to development of therapeutic viruses include disabling viral functions that aim inactivation of antiviral defense mechanisms of normal cells and of the organism, and arming the viruses with additional functions that specifically target cancer cells. We will describe approaches to development of safe and potent therapeutic viruses that would specifically recognize and kill cancer cells. We will emphasize the need of personalized prediction of sensitivity of patient’s tumors in order to select efficient sets of oncolytic viruses. We propose that oncolytic viruses could efficiently “hunt” for cancer cells, as genetically unstable oncolytic viruses could efficiently win the genetic competition with somewhat less unstable cancer cells and overcome the problem of therapy-induced resistance.