The current phase of opioid overdose deaths in the U.S. is marked by a sharp increase in fatalities, primarily driven by the rise of synthetic opioids like fentanyl. In recent years, fentanyl has become the leading cause of opioid-related overdose deaths, contributing to a growing crisis. While overdose deaths from prescription opioids have stabilized or declined due to regulatory measures, fentanyl's presence in the illicit drug supply has led to a dramatic surge in deaths, often involving users unknowingly consuming fentanyl-laced substances. Fentanyl's impact extends beyond opioid users, particularly affecting those who use stimulants like cocaine and methamphetamine. Many stimulant users are now at risk of overdose due to fentanyl contamination in their drugs, which significantly heightens the potential for accidental overdose and death. For treatment, this complex crisis requires multifaceted approaches, including the expanded use of medication-assisted treatment (MAT) with buprenorphine or methadone for opioid addiction, naloxone distribution to reverse overdoses, and harm reduction strategies like fentanyl testing strips. In addition, clinicians are increasingly focusing on addressing the unique needs of stimulant users who face the dual challenge of stimulant use and potential opioid contamination, with integrated treatment approaches that combine behavioral therapies and MAT for co-occurring addiction disorders.