The concepts of stress and distress are integral parts of consideration of animal well-being. Generally, stress refers to a state of threatened homeostasis, but precise clinical definitions, causes, and biological measurements have been controversial and confusing. Numerous factors associated with needs, life in captivity, threatening events, or aversive stimuli may threaten homeostasis. An animal's well-being or quality of life is an individual's internal somatic and mental state that is affected by what it knows or perceives; its feelings and motivational state; the responses to internal or external stimuli or environments; interacting variables; and phylogeny and ontogeny. Threats to homeostasis activate a complex pattern of behavioral changes and responses in the central and autonomic nervous and endocrine systems. Some responses can be considered normal adaptive and coping activities, satisfactorily handling the threats and therefore contributing to well-being. Other responses may be considered abnormal, maladaptive, and affective disorders. A persistent threat may lead to prolonged hyperactivity of the neuroendocrine system, which impairs rather than contributes to well-being. Except for extremes, differentiation between normal and abnormal internal states is frequently unclear. Individual adapting and coping styles may be more important than the stimuli in determining the varied responses. In animals, perception of a stimulus or life event is as important as the actual situation or environment. As caregivers, humans may know that an event or situation is no threat, but the animal usually does not function with the same information base as humans. A principal component in controlling an animal's response to an external event is determining how the animal perceives a situation. Mental and biological well-being is more likely to exist in animals if they are familiar with their environment, including social groups, and if they can predict or anticipate changes in the environment.