Clinicians often have excitable optimism, enthusiastically embracing new drugs that have been demonstrated to improve patient outcomes, especially in oncology. 1 Furthermore, involvement in proving the efficacy and safety of a new treatment through clinical research is often a major positive when considering a career path in oncology. 2 As emphasized in the article that accompanies this editorial, 3 do we, clinicians, really understand the gargantuan amount of international work behind the development and validation of a new drug? Indeed, to use a new, better drug, we have to stand on the shoulders of the very many scientists who have provided, in a gated stepwise process, sound experimental, translational, pharmacologic, and toxicologic evidence to support the costly development of a novel medication. 4 Bench-to-bedside drug research is even more relevant for first-in-class drugs, defined as the first to be approved for a particular target or mechanism of action, representing a novel approach to treating a condition or disease. [5][6][7] These drugs can then pave the path for next-inclass or subsequent drugs with a similar mechanism of action. 8,9 Clinician oncologists typically have an awareness of the bottleneck associated with steps in research for a first-in-class drug development. This includes the identification of a relevant target, previously undrugged, through pinpointing of the molecular mechanisms involved, chemical drug screening/creation, in silico modeling, associated biomarker selection, and the accurate definition of preclinical pharmacotoxicology determinants. [10][11][12][13] All these steps are necessary before even commencing first-in-human clinical testing which proceed from phase 0, I, II trials to the gold-standard randomized controlled phase III trial typically required for regulatory approval. 14 Clinicians often are keenly aware that the process does not even stop after approval as postmarketing phase IV evidence is also important. 15 Even when a new drug is licensed, the role of oncologists is to further optimize its use, integrating it into the therapeutic arsenal against a specific disease or condition. This can be nuanced and examples include the definition, even through mathematical modeling, of its optimal place in a combinational or sequential pathway of existing therapeutics, the integration within oncosurgical or chemoradiotherapy approaches, the identification of pharmacogenomics determinants, and characterization of the optimal time-of-day administration. [16][17][18][19][20][21] Before this clinical optimization process can start, the new first-in-class drug needs to be developed and approved. The manuscript by Ronquillo et al 3 shows, in an elegant and modern way, the timespan associated with the journey from the very first step to US Food and Drug Administration (FDA) approval. Their description and quantification of the real-life landscape of first-in-class drug development is of broad interest because of both its content and the methodology.Regarding the content, they sh...