Chemical probes are selective small-molecule modulators, usually inhibitors, of their target protein’s function, that can be used in cell or even animal studies to interrogate the functions of their target proteins. Cheryl Arrowsmith, the leader of a new initiative called Target 2035, which seeks to identify a pharmacological modulator for most human proteins by the year 2035, and Paul Workman, the Executive Director of the nonprofit Chemical Probes Portal, an online resource dedicated to chemical probes, talked to Nature Communications about chemical probes, their respective paths to leadership positions in the field, the online resources available to those interested in the topic and the promise and value of open — collaborative — science. The below material is a modified transcript of a long discussion, preserving the conversational tone, but streamlined and edited for clarity, and thus we do not attribute the particular parts to Cheryl or Paul specifically except for when they shared their personal experiences.