The resistance to anticancer drugs (cytotoxic compounds and molecular targeted agents) and radiotherapy is the main obstacle for an effective treatment of human cancers. This limitation to the success of cancer treatment has led to the study of the molecular mechanisms underling drug resistance as well as to the development of novel combinatorial strategies which can overcome the acquired and intrinsic resistance. In this book by presenting novel mechanisms of drug resistance two different lines of research are analyzed: a) The molecular basis of resistance to the treatment with the novel inhibitors of the tyrosine-kinase encoded by the mutated form of the gene BRAF in melanoma carrying the mutant BRAF V600E and potential therapeutic strategies to counteract this resistance. b) The role of specific inhibition of PARP1 enzyme to potentiate the cytotoxicity of chemo-radiotherapy in human glioblastoma cells. The analysis of the presented results should help to shed some light on this timely and clinically relevant topic, and should be especially useful to students as well as medical doctors, or anyone else who may be interest in cancer research or treatment.