The broad and potent activity of piperazine has established it as one of the biologically important scaffolds. This article is an effort to highlight the importance of the piperazine in the present context and promise they hold for the future. This review mainly focused the updated information on the most active piperazine derivatives that have been reported to show significant biological actions for instance anti-microbial, anti-depressant, anticonvulsant, anti-parkinson, anti-inflammatory, antipsychotic, antioxidant, antidiabetic, antiarrhythmic, antiproliferative, anxiolytic, antialzheimer, antimalarial, antihypertensive, antiplatelet aggression and anti-histaminic activity. This review would take on benzylpiperazine (BZP) and trifluoromethylpiperazine (TFMPP), benzhydryl piperazine, diphenylalkyl piperazine, phenyl piperazine as the most popular member of the piperazines, focusing the discussion on their origins, pharmacokinetics and pharmacodynamics, and their effects on the human body. From these outcomes, information for future molecular modifications leading to compounds with greater positive pharmacological properties may be derived.