The mechanisms of genetically determined mechanisms of resistance to several target drugs were discussed in breast cancer, melanoma, colorectal and prostate cancers, chronic myelogenous leukemia, small cell lung cancer, and medulloblastoma. In each case, heterogeneity of mechanisms was emphasized. In melanoma, therapeutic interference with the effects of BRAF mutations was repeatedly discussed. It was also reported that anti-CTLA4 antibodies provided the first treatment improving survival of patients with stage IV melanoma. Epithelial-mesenchymal transition (EMT) was introduced as a mechanism of resistance, particularly in lung and pancreatic cancer, where the role of microenvironment factors was also indicated. In colorectal and prostate cancers, the use of liquid biopsies, namely, measurements of tumor nucleic acid in blood, were indicated as a way to obtain whole-tumor assessment instead of the partial assessment obtainable with traditional biopsies. Knowledge of the mechanisms of drug action and resistance was stressed to be essential for the design of new agents and combination of agents aimed at increasing antitumor effectiveness and overcoming resistance.