PURPOSE OF REVIEW: The aim of this review is to provide an update on recent trends of New Psychoactive Substances (NPS) and the current global strategies implemented to manage them. RECENT FINDINGS: The number of NPS has increased from 166 in 2009 to 892 in 2018, with about 36% having stimulant effects. Such trend revels some unprecedented patterns. The decline in the emergence of new synthetic cannabinoids has coincided with rising deaths due to overdose of fentanyl and non-fentanyl compounds in North America and Europe. The detection of new stimulant NPS has stabilized since 2015. Although the level of seizures of mephedrone have risen since then, they are still below the levels reported before international control. The legal status of kratom still remains unclear, whereas calls for research on its benefits continue. The nonmedical use of tramadol in Africa and Middle East is a cause of growing concern. SUMMARY: Although the rise of NPS is a cause for concern, evidence suggests that the strategy to face the challenge should include updating international data collection systems, integrating scientific-based interventions for drug use, strengthening national monitoring, and increasing collaborative research and forensic capabilities. The legal, regulatory framework and clinical guidelines should remain dynamic, whereas enforcement agencies should measure success by destroying drug networks as seizures rarely dismantle drug markets.