Recent United States alerts on fentanyl analogues, medetomidine, cychlorphine, drug mixtures and concentrated 7-OH products highlight evolving challenges across the substance use workforce. They invite us to review local preparedness, understand testing limitations and strengthen links between frontline services, laboratories and public-health partners. A useful response brings together clinical, prevention, recovery and peer perspectives, with clear responsibilities for turning relevant findings into action. For the global ISSUP community, these alerts offer lessons in preparedness while requiring careful consideration of local evidence, resources and service arrangements. Staying informed through trusted sources and sharing practical responses through ISSUP can help translate emerging knowledge into safer care and more responsive support for individuals, families and communities.