The inhibition of cancer growth and progression is one of the major challenges facing modern medicine. Despite significant progress in the development of therapies against cancer, only in a few cases are these therapies effective. Because cancer is a complex disease, agents that target a single oncogenic pathway have low efficacy, in addition to allowing the emergence of drug resistance. There is a need for specific therapy, which can affect a broad range of cancers, with minimal side effects. Here we summarize several novel anti-cancer strategies that answer the above criteria. These strategies utilize the multiple anti-proliferative effects of double stranded RNA (dsRNA): (1) the classical antisense RNA hybridizes with its target mRNA, leading to reduced levels of a specific oncoprotein; (2) short dsRNA of specific sequence, known as small inhibitory RNA (siRNA), can selectively and efficiently inhibit expression of specific oncogenes, expressed in cancer cells but not in normal cells. Shutting down the expression of cancer-promoting genes by siRNA has proven to be an effective approach against several cancers; (3) long dsRNA, frequently expressed in cells infected with viruses, activates mechanisms that efficiently kill the infected cells, thereby preventing spread of the virus. The dsRNA killing strategy (DKS), involving the in situ generation of dsRNA of sufficient length to induce antiviral defenses specifically in cancer cells, is a novel strategy developed in our laboratory. DKS has the potential to be applicable to a wide range of cancers. Thus dsRNA-based anti-cancer strategies could be powerful tools for cancer treatment.