Tuberculosis is the most relevant infectious disease worldwide according to the estimates of the World Health Organization, and despite being a curable disease, it requires a 6-9-month therapy with multiple antibiotics. Intermittent drug therapy due to noncompliance or poor delivery of therapy promotes the emergence of bacterial strains showing resistance to multiple drugs and the rise of extremely drug-resistant strains. Moreover, increased antibiotic resistance has been observed for several microorganisms, including extremely drug-resistant tuberculosis, vancomycin-resistant Enterococcus faecalis, or methicillin-resistant Staphylococcus aureus. In vitro, cathelicidin induction results in enhanced mycobacterial clearance, and synthetic human neutrophil peptides had a rather modest bactericidal effect in Mycobacterium tuberculosis-infected mice. In vivo therapeutic efficacy of improved molecules that show enhanced bactericidal action in vitro remains to be tested.