Simple Summary: Behavioral problems and medical conditions have been treated separately for years. However, behavior depends directly on an animal's health condition, and vice versa. Some behavioral problems are caused totally or partially by a medical condition. Additionally, some of these problems represent a diagnostic challenge for veterinarians because, in many cases, apart from behavioral changes, there are no other clinical signs or evidence of illness. Improving our knowledge of the most common medical problems that can modify behavior may help veterinarians to improve their diagnostic protocols and treatments. Based on our experience, most relevant medical conditions are some neurological problems, endocrine or metabolic problems, and pain-related conditions. Thus, the aims of this review are to describe the state of the art of the relationship between these medical conditions (among others) and behavioral problems, and proposing new lines of investigation.Abstract: Not all animals behave identically when faced with the same situation. These individual differences in the expression of their behavior could be due to many factors, including medical conditions. These medical problems can change behavior directly or indirectly. The aims of this review are to describe the state of the art of the relationship among some medical and behavioral problems, and to propose new lines of investigation. The revision is focused on the relation between behavioral problems and pain, endocrine diseases, neurological problems, vomeronasal organ alterations, and cardiac disorders. These problems represent a diagnostic challenge from a practical point of view. The most common sign of pain in animals is a change in behavior. Although the relation of pain to behavioral problems has been widely studied, it is not absolutely clear. As an example, the relation between sleep disorders and pain is poorly known in veterinary medicine. New studies in humans and laboratory animals show that a reciprocal relationship does, in fact, exist. More specifically, the literature suggests that the temporal effect of sleep deprivation on pain may be stronger than that of pain on sleep. Some behavioral problems could modify the sleep-awake cycle (e.g., cognitive dysfunction). The impact of these behavioral problems on pain perception is completely unknown in dogs and cats. Thyroid hormones play an important role, regarding behavioral control. Both hypothyroidism and hyperthyroidism have been related to behavioral changes. Concerning hypothyroidism, this relationship remains controversial. Nonetheless, new neuro-imaging studies provide objective evidence that brain structure and function are altered in hypothyroid patients, both in laboratory animals and in humans. There are many neurological problems that could potentially change behavior. This paper reviews those neurological problems that could lead to behavioral changes without modifying neurological examination. The most common problems are tumors that affect central nervous system silent zon...