Obstructive Sleep Apnea (OSA) is a prevalent sleep disorder characterized by repeated upper airway obstructions during sleep, leading to intermittent hypoxia and sleep fragmentation. This chapter examines the pathophysiology of OSA, focusing on the interplay of anatomical vulnerabilities, neuromuscular deficits, and systemic responses. Animal models, including rodents, rabbits, dogs, and non-human primates, are instrumental in advancing our understanding of OSA mechanisms and therapeutic strategies. Rodent models replicate key features of OSA, such as oxidative stress and cardiovascular dysfunction, while rabbit models offer insights into upper airway dynamics. Larger mammals like dogs and primates provide translational relevance due to their anatomical and physiological similarities to humans. Naturally occurring OSA in brachycephalic dogs mirrors human disease, offering unique opportunities for studying disease progression and testing interventions. These findings elucidate the importance of animal models in bridging basic research with clinical applications to improve OSA management.