The outcome of infection with Mycobacterium tuberculosis (MTB) is largely influenced by the host-pathogen interaction in which both the human host and the MTB genetic backgrounds play an important role. Whether this interaction also influences the selection and expansion of drug-resistant MTB strains is the primary focus of this review. We first outline the main and recent findings regarding MTB determinants implicated in the development of drug resistance. Second, we examine data regarding human genetic factors that may play a role in TB drug resistance. We highlight interesting openings for TB research and therapy. (C) 2016 Elsevier B.V. and International Society of Chemotherapy. All rights reserved.