The Five Domains Model has been used to guide assessment of animal welfare for 25 years and has been regularly extended and updated during that time to reflect evolution of thinking and knowledge about animals and their welfare. Using the model, information about the observable/ measurable state of the animal is compiled in four physical/functional domains relating to its: 1. Nutrition/Hydration; 2. Physical Environment; 3. Health; and 4. Behavioural Interactions. This information is then used to cautiously infer the animal’s likely mental experiences, which are most relevant to its welfare state, in Domain 5: Mental State. Negative experiences such as thirst, hunger, breathlessness or pain arise in Domain 5 from factors that disturb or disrupt the internal stability of the body (evidence in Domains 1-3) or when the animal is stopped from achieving strongly motivated behavioural goals to interact with the environment and other animals, e.g. fear or frustration (evidence in Domain 4). Positive experiences such as pleasures of eating or thermal comfort may arise when the animal has opportunities to maintain or restore its internal physical stability (Domains 1-3) or when it can achieve its goals, e.g. pleasure and safety of companionship (Domain 4). The latest version of the model focusses attention on the welfare implications of animals’ various interactions with humans, primarily through evidence compiled in Domain 4. This extension of the model and illustrations of the mental experiences arising from animal-human interactions will be useful for those caring for animals in a wide range of contexts.