Trypanosomatids continue to cause suffering among human and wide range of animal population and have enormous health, social and economic impact. The present constraints in control of trypanosomosis are availability of limited number of effective drugs with narrow safety index, nonavailability of vaccines due to immune evasion mechanisms developed by the parasite and drug resistance problem. The kinetoplastids/ trypanosomatids possess unique kinetoplast DNA structure and express hundreds of membrane transport proteins that allow them to take up nutrients, establish ion gradients, efflux metabolites, translocate compounds from one intracellular compartment to another, and take up or export drugs. In this context, there is urgent need of application of innovative strategies for identification of novel therapeutic drug targets affecting metabolic pathways essential for survival of the parasites using modern molecular approaches (functional/genomics/ proteomics/bioinformatics). In this review we have discussed existing drugs in use for treatment and outline of emerging approaches in identification and evaluation of potential novel therapeutic targets against trypanosomatids.