Animal models of ventilator-associated pneumonia (VAP) represent a unique scenario for the study of the different aspects of human VAP. Several years of investigation have yielded important information regarding: the understanding of lung and systemic inflammatory responses to pneumonia and potential therapeutic modulation; the different diagnostic sampling methods with the advantage of having a gold standard for microbiology and histopathology of lung samples; clinical efficacy of intravenous and aerosolised antimicrobials and their pharmacokinetic parameters in lung disease infections; how pneumonia affects the different patterns and modes of mechanical ventilation; and the study of preventive measures in VAP. This chapter focuses on: the basic principles of animal model VAP preparation; how the above-mentioned aspects are studied; and how more realistic results are produced and how their translation into clinical practice can occur.