Based on previous reports and events, we attempted to demonstrate how to achieve sound, reliable clinical development, particularly in this new area where the oncologist will be faced with the dilemma of choosing the most appropriate chemo-radiotherapy combination for use in routine clinical practice in the near future. Data were obtained by searches of MEDLINE, PubMed, and references from relevant English-language articles. Among the different strategies aimed at improving therapy, drug-radiation combinations have the strongest impact on current solid tumor treatment practice. However, developing a new strategy combining RT and drugs without preclinical development and sufficiently solid data is prohibited. Preclinical phase should be considered a prerequisite for optimizing the success of the clinical phases in the interest of patients, oncologists and also of pharmaceutical companies, thereby avoiding pointless and sometimes expensive toxic trials. A caveat is directed at radiation oncologists, at the expense of scientific reliability and validity which surely, should not be compromised.