In various types of malignancies, conventional forms of therapy (surgery, radiation and chemotherapy) are often ineffective, as well as harmful. In the last few years, a convergence of scientific advances has enabled the identification of molecular targets and signaling pathways specific to cancer cells, resulting in therapies with enhanced selectivity and efficacy and reduced toxicity. Compound validation has relied on target validation first, although some of the most successful drugs often have effects outside of their postulated mechanism. Protein kinases represent such molecular targets; considerable research effort has been devoted to the development of targeted drugs that inhibit the action of pathogenic kinases, and clinical studies performed so far have validated the positive effects of kinase inhibitors for cancer treatment. In this review, the specificity, mechanism of action and antitumor activity of several new small-molecule inhibitors of tyrosine and serine/threonine kinases are discussed.