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Multidrug resistant microorganisms (MDROs) have been responsible for numerous outbreaks of infectious epidemics, and pose a serious threat to global health. The lack of effective therapies for these MDROs, coupled with a reduced number of antimicrobial drugs in the pharmaceutical pipeline to treat these infections indicates an urgent need for research in this area. Of the resistant Gram-positive bacteria, methicillin-resistant Staphylococcus aureus (MRSA), multidrug-resistant Pseudomonas aeruginosa and multidrug-resistant tuberculosis (MDR-TB) continue to be the most problematic, but more recently there has been increasing reports of vancomycin-resistant Staphylococcus aureus (VRSA) infections. For highly-resistant Gram-negative bacteria, Vancomycin-resistant Enterococci (VRE), multidrug-resistant carbapenemase-producing Klebsiella pneumoniae and MDR-Acinetobacter baumannii are important as these bacteria are often only susceptible to older antimicrobial agents, such as the polymyxins that have a higher adverse event profile. Thus, there is an urgent need for new antibiotics and combinations of drugs to treat these emerging MDR bacteria. The lack of interest by pharmaceutical companies in the research and development of new antibiotics has increased research in the field of natural products. An increasing body of scientific evidence suggests that specific marine, fungal and medicinal plant extracts, as well as traditional medicine formulas and purified natural products are active against specific MDR-bacteria, and thus could be further investigated and possibly developed as clinical agents. This review focuses on recently published data for natural products active against MDR bacteria and evaluates some of the recent published in vitro data.