Objectives. To examine trends in overdose deaths by intent and drug category to better understand the recent decrease in overdose suicides amid the overdose epidemic. Methods. We examined trends in rates of overdose deaths by intent (unintentional, suicide, or undetermined) across 9 drug categories from 1999 to 2022 using US National Vital Statistics System mortality data. Results. Unintentional overdoses involving synthetic opioids, polydrug toxicity involving synthetic opioids, psychostimulants, and cocaine increased exponentially with annual percentage changes ranging from 15.0% to 104.9% during 2010 to 2022. The death rates also increased for suicides involving these drugs, especially for psychostimulants (annual percentage change = 12.9% for 2010-2022; P < .001). However, these drugs accounted for relatively small percentages of overdose suicides. The leading drug categories among suicides were antidepressants, prescription opioids, and benzodiazepines, though these deaths have decreased or leveled off in recent years. Conclusions. Different drugs commonly involved in suicides and unintentional overdoses may contribute to their divergent trends. Public Health Implications. Amid the overdose epidemic, safe storage of medications remains a crucial strategy to prevent overdose suicides. The large increases in suicides involving psychostimulants warrant monitoring. (Am J Public Health. 2024;114(10):1081-1085. https://doi.org/10.2105/AJPH.2024.307745).