NPSs make up a diverse and growing group of new compounds. They are usually derivatives or analogues of previously known recreational drugs that have been produced to achieve the same effect and have circumvented legal regulation. Despite a general decrease in the number of newly identified substances, approximately 400 previously notified NPS are confinned annually. This finding suggests that many substances remain on the market longer after they appear and need to be monitored systematically. In this paper, the division of NPSs into four groups was adopted: synthetic stimulants, synthetic cannabinoids, synthetic hallucinogens, and synthetic depressants. The chemical structures and mechanisms of action recorded so far have been reviewed. Small changes in structure have an impact on their pharmacological properties, even within the same group, making it difficult to predict effects, potency, and toxicity. Available papers on the effects of NPSs and guidelines for therapy have emerged from smaller case studies. Treatment mainly includes monitoring of the patient's clinical picture and symptomatic and supportive therapy. The available immunochemical analytical methods of targeted screening are not sufficiently sensitive due to the great structural diversity of the NPSs themselves, nor specific due to cross-reactivity with other substances. ln clinical practice more specific confirmation methods such as mass spectrometry coupled chromatography are most often required. In conclusion, the main issues surrounding NPSs are the unknown and unpredictable effects on human health, the lack of rapid analytical detection and the speed of placing newer analogues on the market to avoid legal restrictions.