Tuberculosis is still a terrible human disease, killing over 1 million people every year worldwide. Better antibiotics that could shorten treatment duration and provide a relief to the emergence and spread of drug-resistant strains are definitely needed. In this chapter, we give an overview of the phenotypic screening systems available for drug discovery in tuberculosis, highlighting their potential strengths and weaknesses. In addition, we illustrate with examples how phenotypic screenings have contributed to the field, discuss the role they can play in the future and how some specific gaps could be addressed.