Therefore, this review article aims to create new perspectives to design and develop new anti-TB drugs against multi-drug resistant strains. We will focus on the challenges and advances in antitubercular drug discovery involving MDR-TB. In order to describe those most promising compounds, we included here only active compounds against MDR-TB with minimum inhibitory concentrations (MICs) inferior to 11 µM and low toxicity published in the last 4 years in the following databases: PubMed, Web of Science and Scopus. All MIC values against MDR-TB strains presented herein were converted to µM in order to establish a comparison among the compounds.