Tegumentary leishmaniases (TL) comprise various clinical forms, in which current therapeutic treatments lack in safety and efficacy. Recently the parasite is developing resistance mechanisms against anti leishmanial drugs startling the scientific community to recruit efforts to search for novel therapeutics. Proteomics hold promises for the treatment of leishmaniasis and investigation of parasite–host interaction since these set of methodological tools have provided a wealth of protein expression data on several Leishmania species. Firstly this review puts together the current treatment and challenges to fight tegumentary leishmaniasis. In addition, the 2 dimensional gel electrophoresis and mass spectrometry techniques in protein identification and characterization are described and discussed in the context of proteomics regarding Leishmania studies. In this review, we selected literature content on TL causative agents. Important proteomic findings related to differentiation proteome (promastigote and amastigote forms), Leishmania-macrophage interaction proteome and secreted and soluble proteins including molecules involved in parasite resistance and potential drug targets are examined and discussed. We also highlight open questions regarding drug research that can be addressed with proteomics approaches.