The poor pharmacokinetic profile and toxicity produced by the drugs currently used to treat trypanosomiasis requires an immediate attention for the development of safe, economical and high affinity chemotherapeutic agents to meet the need for this class of drugs. The unacceptable truth is the lack of attention of the government and less interest of pharmaceutical companies in light of less monitory gain in the area of protozoal infection since most of the affected people belong to poorer country. Surprisingly the endeavors of different research group discussed in this review belong to academic institutions. It is felt by the researchers that the treatment for HAT requires a combined approach by government organization, pharmaceutical companies and academic institutions. The most promising fact is that in the last decade several synthetic approaches have been made in the field of development of anti-trypanosomal therapies. Several compounds are being synthesized that yield new compounds for the treatment of HAT, as a result of these synthetic approaches newer leads have been identified, which are under different phase of drug development.