In Indonesia, a country with stringent drug laws, psycho-active prescription drugs (PPDs) have become popular among urban youth as they are seen to be safe – both medically and in terms of the risks of being arrested. During the ChemicalYouth project, which involved a multi-sited ethnography in urban centers in South Sulawesi (Makassar, Gowa, and Maros) and in Yogyakarta, we found that young people encourage each other to try out different kinds of PPDs to determine which (combinations) work best for them. Sharing their experiences, they jointly build up knowledge that guides their ‘experimental trajectories’ (Raikhel and Garriott 2013). The experimental trajectories of youths are enabled by pharmacies, where young people can buy PPDs, and private sector doctors who sell and prescribe PPD prescriptions. When certain PPDs become harder to get, young people will try out new substances in their search for happiness, highs, and the confidence and stamina needed to perform precarious informal sector jobs such as sex work, street singing, and helping people park their cars. Across the sites, the researchers encountered young people realizing that they had become addicted to PPDs. Simultaneously, health workers lack instruments to prevent harm related to PPD use as they work in public sector harm reduction programs designed narrowly to address illicit heroin addiction. We argue that educational interventions need to address the desires and aspirations for good enough lives that are reflected in young people’s creative poly-drug use practices, and the iatrogenic effects of unregulated pharmaceutical markets that enable medicalization of precarious lives.