Phage therapy refers to the use of bacteriophages (phages - bacterial viruses) as therapeutic agents against infectious bacterial diseases. This therapeutic approach emerged in the beginning of the 20th century but was progressively replaced by the use of antibiotics in most parts of the world after the second world war. More recently however, the alarming rise of multidrug-resistant bacteria and the consequent need for antibiotic alternatives has renewed interest in phages as antimicrobial agents. Several scientific, technological and regulatory advances have supported the credibility of a second revolution in phage therapy. Nevertheless, phage therapy still faces many challenges that include: i) the need to increase phage collections from reference phage banks; ii) the development of efficient phage screening methods for the fast identification of the therapeutic phage(s); iii) the establishment of efficient phage therapy strategies to tackle infectious biofilms; iv) the validation of feasible phage production protocols that assure quality and safety of phage preparations; and (v) the guarantee of stability of phage preparations during manufacturing, storage and transport. Moreover, current maladapted regulatory structures represent a significant hurdle for potential commercialization of phage therapeutics. This article describes the past and current status of phage therapy and presents the most recent advances in this domain.