Panic disorder (PD) is characterized by recurrent and uncontrollable panic attacks associated with behavioral changes and/or persistent anxiety due to the attacks. The development of behavioral models in animals is important for the understanding of the psychobiological and behavioral bases of PD. The present article reviews the main models used in the current literature. Biobehavioral assays used in rats and mice include fear conditioning (which presents moderate predictive, face, and construct validities); the elevated T-maze (which presents good predictive validity, but low face and construct validities); electrical stimulation of the periaqueductal gray (which presents good face validity, but moderate construct validity); predator exposure models (which present good predictive and moderate construct validity); and hypercapnia-induced responses (which present moderate construct validity). These three approaches seek coherence with theories on fear as a way to increase its translational potential; thus, while the elevated T-maze is supported by the Deakin/Graeff theory, the mouse defense test battery relies on the concept of defensive distance, and periaqueductal gray stimulation is based on the functional neuroanatomy of fear. Moreover, to higher or lower degree the three models are supported by an “etho-experimental” approach, with careful observation of animal behavior as a way of discriminating different defensive strategies that model different aspects of anxiety, fear, and panic. These assays can be used, in conjunction with independent variables that attempt to simulate the vulnerabilities and stressors which lead to panic attacks, to produce true models of PD. Finally, an alternative/complementary model is proposed that uses zebrafish alarm reaction to study this disorder.