Drugs have been used for recreational purposes since time immemorial. Addicting potential and the propensity to harm has led to a ban on many of these drugs. New compounds are being developed to circumvent the ban. They are similar in effect to the banned drugs but are slightly different in their chemical structure so that they can escape detection in the standard drug tests. These drugs are commonly known as designer drugs or new psychoactive substances (NPS).This work aimed to do a comprehensive review on chemistry, pharmacology and toxicology of new designer drugs for establishing the basic knowledge about them, focusing on their assessment and management and recent methods for their detection.According to the United Nations Office on Drugs and Crime (UNODC) classification, NPS include the following groups: Synthetic cannabinoids, synthetic cathinones, piperazine, phenethylamines, ketamine analogues, plant-based substances(Kratom, Salvia Divinorum) and miscellaneous substances (aminoindanes and tryptamines). NPS have become a global phenomenon with over 100 countries and territories from all regions of the world having reported one or more NPS. Up to December 2015, more than 600 substances have been reported to the UNODC Early Warning Advisory (EWA) on NPS by Governments, laboratories and partner organizations.NPS represent a challenge both in forensic analytical toxicology as well as in clinical toxicology as they may cause serious toxicity and can escape detection in the standard drug tests.Clinicians should keep designer drugs in mind when evaluating substance use in young adults or in anyone presenting with acute neuropsychiatric complaintsCoordination among emergency medical personnel, forensic toxicologists, scientific researchers, law enforcement and policymakers is essential to foster more effective responses in dealing with this evolving drug-abuse phenomenon