Attrition rates of drugs from human entry to regulatory approval are far higher in anticancer drugs than those for nononcology indications. In the era of molecular therapeutics that results from a deeper understanding in cancer biology and advancing technologies, the number of compounds available for clinical testing is likely to continue to increase. Although the main objectives of phase I trials are to characterize toxicities of new agents and to determine the recommended dose for phase II development, most phase I studies are now designed to provide some early signal on preliminary efficacy as secondary objectives. The "go-no-go" decision to further develop a drug, or not, is now often pushed forward to the phase I setting. Thus, there is a need for investigators to be able to critically review the preclinical data available in order to determine which drugs should advance on the developmental path. This review highlights the intrinsic characteristics of a drug and the relevant data to be collected during its preclinical assessment, which may maximize the chances of success in clinical testing and eventual regulatory approval.