Although they diverge in objectives, probes for chemical biology and leads for drug discovery converge in some of their desirable attributes. However, we can use an empirical definition that biological system insights, in vitro and in vivo, along with advantageous property profiles are the primary goals for probes. For drugs, the therapeutic outcome in human patients is obviously the overriding objective (and by definition also for ADEV). Notwithstanding, drugs need characterising by probing biological systems to determine not only the mechanistic basis of therapeutic efficacy but also that their non-efficacious effects are understood well enough to be acceptable (e.g. the systems pharmacology characterisation offered by SciLifeLab DDD). Drug candidates must be mandatorily tested in rodents but relevant mechanistic insights (even unpredicted ones) may also be generated from phylogenetically wider probing experiments (e.g. assessing functional perturbations) in yeast, C.elegans, Zebrafish or more recently characterised non-standard model organisms.