The proliferation from traditional drugs to designer drugs presents significant challenges for forensic scientists. The rapid emergence as well as diverse chemical structures of designer drugs poses significant challenges for regulatory authorities and forensic scientists. Although, several common and sophisticated methodologies exist which provide high sensitivity and specificity for the accurate detection of various drugs in different matrices, identification and detection of designer drugs is herculean task for investigators. Despite advancements in forensic methodologies, several challenges even persist in the seizure and identification of designer drugs in fields for Investigating Agencies. A productive collaboration between forensic scientists, regulatory agencies, and institutions would be able to successfully combat the dynamic nature of new psychotropic substances.