This chapter explores translational challenges in the era of precision or personalised medicine, which is also called “P4 medicine”. It argues that preventive strategies within the P4 (personalised, predictive, preventive, participatory) framework may aim to translate ‘risks’ into benefit without a real target audience in mind; that is, in ways that do not fit personal and societal contexts, or that are premature. In this way, it risks resulting in waste and harm. To improve this situation, the authors argue that the challenges that human-level complexity poses for personalised medicine should be better accounted for, also in initial phases of medical translation.