Drug discovery research is a complex undertaking conducted by teams of scientists representing the different areas involved. In addition to a strong familiarity with existing knowledge, key relevant concepts remain unknown as activities start. This is often an accepted risk, mitigated by gaining understanding in real time as the project develops. Chemicals play a role in all biology studies conducted in the context of drug discovery, whether endogenously or exogenously added to the system under study. Furthermore, new knowledge often flourishes at the interface of existing areas of expertise. Due to differences in their training, adding a chemist's perspective to research teams would at least avoid potentially costly mistakes and ideally make any biology research richer. Thus, it would seem natural that one such team member be a chemist. Still, as that may not always be the case, we present some suggestions to minimize the risk of irreproducibility due to chemistry-related issues during biology research supporting drug discovery and make these efforts more robust and impactful. These include discussions on identity and purity, target and species selectivity, and chemical modalities such as orthosteric or allosteric small molecules or antibodies. Given the immense diversity of potential chemical/biological system interactions, we do not intend to provide a foolproof guide to conduct biological experimentation. Investigate at your own peril!