Aim of the present review of various classic and novel therapeutic strategies in oncology is critical discussion of its efficacy to answer whether once upon a time is it real and possible to win a war against cancer. Although technological progress in radiotherapy (RT) has led to develop many sophisticated 3D, 4D techniques, the use of the RT as a sole modality has become more and more limited to the tumours in early stage of disease, in favour of combined surgery-RT-chemotherapy (CHT) therapies. Nevertheless patients curability has never reached the level higher than 95% (stereotactic hypofractionated RT – limited too small tumours only). The CHT for solid malignant tumours is not effective enough, and therefore it is mainly combined with Surg and RT as a method of the boost. Common use of partial or complete regression (PR, CR) as end-points of its efficacy is irrelevant, since it is quasi-quantified tumour cell clearance but not cell kill effects, and the regrowth delay (time of tumour regrowth to the size, volume at the beginning of therapy) is the only proper end-point. Efficacy of various genetic, molecular, immuno, and antiangiogenic modalities tested in many clinical studies is critically discussed, and it has generally showed some therapeutic benefits, but not very spectacular. It has been well documented that genotypes and phenotypes of the tumours (even within the same location, stage and histology) are individually highly heterogeneous. Therefore, the term “average probability” referred to individual patients becomes meaningless, and moreover, this term has never been replaced by “certainty” yet. Statistics of many studies and trials consist of various pitfalls and biases. Thus, although we and our patients are more often winners on the individual battlefields, the winning once upon a time of whole war against cancer seems to be possible (hope), but not for sure (real).